Application of banana extract in improving sensitivity of cancer cells to anti-cancer drugs

Abstract

The invention relates to application of banana extract in improving sensitivity of cancer cells to anti-cancer drugs. The banana extract disclosed by the invention can be used for improving the sensitivity of cancer cells to anti-cancer drugs.

Description

Technical Field

[0001] The present invention relates to using banana extract to enhance the sensitivity of cancer cells to anticancer drugs. Background Art

[0002] Anticancer drugs are classified into chemotherapeutic drugs (e.g., 5-FU and Gemcitabine) with no specific cytotoxicity and targeted drugs (e.g., Gefitinib) that interfere with specific molecules involved in cancer cell survival according to their mechanism of action. However, cancer cells may develop drug resistance to both drugs, which greatly reduces drug sensitivity and efficacy. Therefore, researchers in this field have been committed to developing methods that can increase the sensitivity of cancer cells to anticancer drugs and / or reduce drug resistance.

[0003] Banana (Musa paradisiaca; Banana) is a herbaceous plant of the genus Musa in the family Musaceae. The fruit is the main utilizable part. Studies have shown that banana has anti-inflammatory and antioxidant pharmacological effects. In addition, in SS Dahham et al., (2015), Acad. J. Cancer Res., 8:28-34, hexane extracts of banana peel and pulp were found to have effects against colorectal cancer and breast cancer.

[0004] TW I584814B discloses a method for extracting banana stems, leaves and barks using saline solution with a volume percentage of 5% to 40%, a banana extract obtained by the method, and an antibacterial application of the banana extract.

[0005] As far as the applicant is aware, there is no document or patent case that has ever disclosed that the banana extract disclosed in TW I584814B can be used to increase the sensitivity of cancer cells to anticancer drugs. Summary of the invention

[0006] After research, the applicant unexpectedly discovered that the banana extract disclosed in TW I584814B itself cannot directly inhibit the growth of cancer cells, but can unexpectedly increase the sensitivity of drug-resistant cancer cells to anticancer drugs (including chemotherapy drugs and targeted drugs), that is, reduce drug resistance. Therefore, the applicant believes that banana extract has a high potential to be developed into a drug that increases the sensitivity of anticancer drugs or treats drug-resistant cancers.

[0007] Thus, in a first aspect, the present invention provides a use of a banana extract for preparing a medicament for increasing the sensitivity of cancer cells to anticancer drugs, wherein the banana extract is prepared by a method comprising the following steps:

[0008] Prepare raw materials, which include banana (Musa paradisiaca) stems, leaves, barks or a combination thereof, and crush the raw materials into extracts to be extracted;

[0009] The extract is immersed in a saline solution with a volume percentage of 5% to 40%, and heated, wherein the volume ratio of the extract to the saline solution is 95:5 to 60:40;

[0010] Extracting the soaked extract by a low-temperature cell wall breaking method to obtain a crude extract, wherein the crude extract contains fiber and liquid;

[0011] Centrifuging the crude extract to separate the fibers from the liquid in the crude extract, filtering the liquid portion and allowing it to stand in a bucket to obtain a crude extract; and

[0012] The crude extract is fermented with far infrared ray stone to obtain banana extract.

[0013] Preferably, the cancer cell is a drug-resistant cancer cell.

[0014] Preferably, the cancer cell is selected from the group consisting of pancreatic cancer cells, lung adenocarcinoma cells, and combinations thereof.

[0015] In a second aspect, the present invention provides a combination for preparing a medicament for treating drug-resistant cancer, wherein the combination comprises an anticancer drug or a pharmaceutically acceptable salt thereof, and the banana extract as described above.

[0016] Preferably, the cancer is selected from the group consisting of pancreatic cancer, lung adenocarcinoma, and combinations thereof.

[0017] Preferably, the banana extract and the anticancer drug are in a single dosage form or separate dosage forms.

[0018] Preferably, the banana extract is in a dosage form for parenteral administration, oral administration or topical administration.

[0019] Preferably, the anticancer drug is in a dosage form for parenteral administration, oral administration or topical administration.

[0020] Preferably, the anticancer drug is selected from the group consisting of Gefitinib, Gemcitabine, Oxaliplatin, 5-FU, and combinations thereof.

[0021] Preferably, in the step of preparing raw materials, the weight ratio of the stem, leaves and bark is 5:3:2 to 6:2:2.

[0022] Preferably, in the step of immersing the extract in saline solution with a volume percentage of 5% to 40% and then heating the extract, the volume ratio of the extract to the saline solution is 70:30.

[0023] Preferably, in the step of centrifuging the crude extract, the crude extract is centrifuged at 3000 rpm (RCF) for 1 minute.

[0024] Preferably, in the step of centrifuging the crude extract and allowing the liquid after filtering the liquid portion to stand in a barrel, the crude extract is 80% to 90% of the upper liquid in the barrel.

[0025] Preferably, the banana extract is liquid, dark golden brown in color, has a specific gravity of 1.12±10%, a viscosity of 1.914±10 centistokes, a boiling point of 104±10°C, and is 100% water-soluble; among the chemical properties of the extract, the pH value is 13, the sodium content is 55,000±10% (mg / kg), the potassium content is 1192±10% (mg / kg), the calcium content is 33±10% (mg / kg), the magnesium content is 26±10% (mg / kg), the zinc content is 9±10% (mg / kg), and the iron content is 9±10% (mg / kg).

[0026] In a third aspect, the present invention provides a method for increasing the sensitivity of cancer cells to anticancer drugs, comprising administering the banana extract as described above to a subject in need thereof.

[0027] In a fourth aspect, the present invention provides a method for treating drug-resistant cancer, comprising administering the combination described above to a subject in need thereof. BRIEF DESCRIPTION OF THE DRAWINGS

[0028] The above and other objects, features and advantages of the present invention will become apparent after referring to the following detailed description and preferred embodiments and the accompanying drawings, in which:

[0029] Figure 1 Shows the effect of banana extract on the survival rate of PANC-1 cells in each group;

[0030] Figure 2 Shows the effect of banana extract on the survival rate of PANC-1 / Gem cells in various groups treated with Gemcitabine, wherein "**" and "***" respectively indicate p<0.01 and p<0.001 when compared with the anticancer drug group, and "##" and "###" respectively indicate p<0.01 and p<0.001 when compared with the corresponding extract group;

[0031] Figure 3 Shows the effect of banana extract on the survival rate of PANC-1 / Gem cells in various groups treated with Oxaliplatin, wherein "**" indicates p < 0.01 when compared with the anticancer drug group, and "#" and "###" indicate p < 0.05 and p < 0.001 when compared with the corresponding extract group, respectively;

[0032] Figure 4 Shows the effect of banana extract on the survival rate of each group of PANC-1 / Gem cells treated with 5-FU, where "*" and "**" respectively indicate p < 0.05 and p < 0.01 when compared with the anticancer drug group, and "###" indicates p < 0.001 when compared with the corresponding extract group;

[0033] Figure 5 Show the effect of banana extract on the survival rate of each group of HCC827 cells; and

[0034] Figure 6 The effect of banana extract on the survival rate of each group of HCC827GR cells treated with Gefitinib is shown, wherein "*" and "**" respectively indicate p < 0.05 and p < 0.01 when compared with the anticancer drug group, and "#", "##" and "###" respectively indicate p < 0.05, p < 0.01 and p < 0.01 when compared with the corresponding extract group. DETAILED DESCRIPTION

[0035] For the purposes of this specification, it will be expressly understood that the word "comprising" means "including, but not limited to," and that the word "comprises" has a corresponding meaning.

[0036] Unless otherwise defined, all technical and scientific terms used in this article have the meaning commonly understood by those skilled in the art. Those skilled in the art will recognize that many methods and materials similar or equivalent to those described herein can be used to implement the present invention. Of course, the present invention is in no way limited to the methods and materials described.

[0037] The present invention provides a use of a banana extract for preparing a pharmaceutical product for increasing the sensitivity of cancer cells to anticancer drugs, wherein the banana extract is prepared by a method comprising the following steps:

[0038] Prepare raw materials, which include banana (Musa paradisiaca) stems, leaves, barks or a combination thereof, and crush the raw materials into extracts to be extracted;

[0039] The extract is immersed in a saline solution with a volume percentage of 5% to 40%, and heated, wherein the volume ratio of the extract to the saline solution is 95:5 to 60:40;

[0040] Extracting the soaked extract by a low-temperature cell wall breaking method to obtain a crude extract, wherein the crude extract contains fiber and liquid;

[0041] Centrifuging the crude extract to separate the fibers from the liquid in the crude extract, filtering the liquid portion and allowing it to stand in a bucket to obtain a crude extract; and

[0042] The crude extract is fermented with far infrared ray stone to obtain banana extract.

[0043] As used herein, the term "increasing the sensitivity of cancer cells to anticancer drugs" means increasing the responsiveness or effectiveness of cancer cells, especially drug-resistant cancer cells, to anticancer drugs.

[0044] As used herein, the term "drug resistance" means that cancer or cancer cells can resist anticancer drugs and have a higher survival rate and lower drug response or effectiveness.

[0045] Cancer cells applicable to the present invention include, but are not limited to, colorectal cancer, acute myeloid leukemia (AML), gastric cancer, breast cancer, pancreatic cancer, and lung adenocarcinoma cancer cells. In a preferred embodiment of the present invention, the cancer cells are selected from the group consisting of pancreatic cancer cells, lung adenocarcinoma cells, and combinations thereof.

[0046] According to the present invention, the preparation of the banana extract can be carried out with reference to the method disclosed in TW I584814B. It can be understood that the operating conditions for the preparation of the banana extract will be further changed with factors such as the banana raw material, the extraction solvent, and the ratio of the two, so as to achieve the best extraction effect. The selection of these operating conditions can be routinely determined by those skilled in the art.

[0047] According to the present invention, in the step of preparing the raw materials, the weight ratio of the stem, leaves and bark can be 5:3:2 to 6:2:2. Preferably, the weight ratio of the stem, leaves and bark is 6:2:2. In some specific examples, the stem is at least 30 kg, the leaves are at least 50 kg, and the bark is at least 20 kg, and the moisture content is below 30%.

[0048] According to the present invention, the stems, leaves and barks can be washed with water and crushed with a crusher to obtain 2 to 3 cm fragments as the extract.

[0049] According to the present invention, in the step of soaking the extract in a salt water with a volume percentage of 5% to 40% and heating, the volume ratio of the extract to the salt water can be 70:30, the soaking can last for 8 to 10 hours, and the heating can be performed with a far infrared ray stone with a spectral wavelength of 7.5μm to 9.5μm. Preferably, the volume percentage of the salt water is 20% to 30%.

[0050] According to the present invention, the low temperature cell wall breaking method can be carried out at a temperature ranging from -40°C to 0°C for 1 to 12 hours. Preferably, the low temperature cell wall breaking method is carried out at -40°C for 6 hours. In some embodiments, the crude extract obtained by the low temperature cell wall breaking method is dark brown, alkaline (pH 12 to pH 14) and has a potential difference of -240 millivolts (mV).

[0051] According to the present invention, in the step of centrifuging the crude extract, the crude extract may be centrifuged at 3000 rpm (RCF) for 1 minute.

[0052] According to the present invention, the filtration of the liquid portion obtained after centrifugation of the crude extract can be performed using a 100 mesh.

[0053] According to the present invention, after filtering the liquid part and letting it stand in the barrel, the obtained crude extract can be 80% to 90% of the upper liquid in the barrel, and the sediment at the bottom of the barrel is impurity waste. Preferably, the standing time in the barrel is 24 hours.

[0054] According to the present invention, the crude extract can be fermented for 90 days with far infrared stones having a spectral wavelength of 7.5 μm to 9.5 μm. In some embodiments, the fermentation is carried out in a fermentation barrel paved with a far infrared stone layer (with a spectral wavelength of 7.5 μm to 9.5 μm).

[0055] In a preferred embodiment of the present invention, the banana extract is liquid, dark golden brown in color, has a specific gravity of 1.12±10%, a viscosity of 1.914±10 centistokes, a boiling point of 104±10°C, and a water solubility of 100%; among the chemical properties of the extract, the pH value is 13, the sodium content is 55,000±10% (mg / kg), the potassium content is 1192±10% (mg / kg), the calcium content is 33±10% (mg / kg), the magnesium content is 26±10% (mg / kg), the zinc content is 9±10% (mg / kg), and the iron content is 9±10% (mg / kg).

[0056] The present invention also provides a combination for preparing a medicament for treating drug-resistant cancer, wherein the combination comprises an anticancer drug or a pharmaceutically acceptable salt thereof, and the banana extract as described above.

[0057] As used herein, "treating" or "treatment" means preventing, reducing, alleviating, ameliorating, relieving, or controlling one or more clinical signs of a disease or disorder, as well as lowering, stopping, or reversing the progression of the severity of the condition or symptom being treated.

[0058] Cancers to which the present invention is applicable include, but are not limited to: colorectal cancer, acute myeloid leukemia, gastric cancer, breast cancer, pancreatic cancer, and lung adenocarcinoma. In a preferred embodiment of the present invention, the cancer is selected from the group consisting of: pancreatic cancer, lung adenocarcinoma, and combinations thereof.

[0059] As used herein, the term "anti-cancer drug" is intended to encompass a variety of existing ingredients or agents that can inhibit the growth of cancer cells or tumors, including chemotherapeutic drugs that are non-specifically cytotoxic and targeted drugs that interfere with specific molecules involved in the survival of cancer cells.

[0060] The chemotherapeutic drugs applicable to the present invention include, but are not limited to: Cisplatin, Doxorubicin, Gemcitabine, Oxaliplatin and 5-FU. In a preferred embodiment of the present invention, the chemotherapeutic drug is selected from the group consisting of: Gemcitabine, Oxaliplatin, 5-FU, and combinations thereof.

[0061] The targeted drugs applicable to the present invention include, but are not limited to: Erlotinib, Osimertinib and Gefitinib. In a preferred embodiment of the present invention, the targeted drug is Gefitinib.

[0062] According to the present invention, the weight ratio of the anticancer drug to the banana extract can be 1:0.15 to 1:7.6. Preferably, when the anticancer drug is Gemcitabine, the weight ratio is 1:0.76 to 1:7.6, more preferably, 1:7.6; when the anticancer drug is Oxaliplatin, the weight ratio is 1:0.5 to 1:5, more preferably, 1:5; when the anticancer drug is 5-FU, the weight ratio is 1:0.15 to 1:1.5, more preferably, 1:1.5; and when the anticancer drug is Gefitinib, the weight ratio is 1:0.22 to 1:2.2, more preferably, 1:2.2.

[0063] As used herein, the term "combination" means the use of two or more active ingredients in combination for co-administering to an individual. In other words, the active ingredients can be combined into a single dosage form or administered simultaneously in separate dosage forms. Alternatively, the active ingredients can also be administered alternately or sequentially in separate dosage forms, and separated by a predetermined time. Preferably, the length of the predetermined time can be adjusted as needed so that the pharmacological effects of the active ingredients in an individual overlap or do not overlap in time. In a preferred embodiment of the present invention, the banana extract and the anticancer drug are administered sequentially.

[0064] According to the present invention, the banana extract and the anticancer drug can be in a dosage form suitable for parenteral administration, oral administration or topical administration.

[0065] According to the present invention, the pharmaceutical product may further include a pharmaceutically acceptable carrier widely used in drug manufacturing technology. For example, the pharmaceutically acceptable carrier may include one or more agents selected from the following: solvent, buffer, emulsifier, suspending agent, decomposer, disintegrating agent, dispersing agent, binding agent, excipient, stabilizer, diluent, gelling agent, wetting agent, lubricant, absorption delaying agent, liposome, extracellular vesicle {such as red blood cell (RBC)-derived vesicle and exosome}-based carrier, nanocarrier and the like. The selection and quantity of these reagents fall within the professional qualities and routine technical scope of those skilled in the art.

[0066] According to the present invention, the banana extract and the anticancer drug can be manufactured into dosage forms suitable for parenteral administration (including injections, for example, sterile aqueous solutions or dispersions) using techniques well known to those skilled in the art, and can be administered by a route selected from the group consisting of: intraperitoneal injection, intrapleural injection, intramuscular injection, intravenous injection, intraarterial injection, intraarticular injection, intrasynovial injection, intrathecal injection, intracranial injection, intraepidermal injection, subcutaneous injection, intradermal injection, intralesional injection, and sublingual administration.

[0067] According to the present invention, the banana extract and the anticancer drug can be manufactured into dosage forms suitable for oral administration using techniques well known to those skilled in the art, including, but not limited to: sterile powder, tablet, troche, lozenge, pellet, capsule, dispersible powder or granule, solution, suspension, emulsion, syrup, elixir, slurry and the like.

[0068] According to the present invention, the banana extract and the anticancer drug can also be manufactured into external preparations suitable for topical application to the skin using techniques well known to those skilled in the art, including, but not limited to: emulsions, gels, ointments, creams, patches, liniments, powders, aerosols, sprays, lotions, serums, pastes, foams, drops, suspensions, salve and bandages.

[0069] In addition, the present invention provides a method for increasing the sensitivity of cancer cells to anticancer drugs, comprising administering the banana extract as described above to a subject in need thereof. The present invention also provides a method for treating drug-resistant cancer, comprising administering the combination as described above to a subject in need thereof.

[0070] As used herein, the terms "administration" and "administration" are used interchangeably and mean introducing, providing or delivering a predetermined active ingredient to a subject by any appropriate route to perform its intended effect.

[0071] As used herein, the term "subject" means any mammal of interest, such as humans, monkeys, cows, sheep, horses, pigs, goats, dogs, cats, mice, and rats.

[0072] The present invention will be further described with reference to the following examples, but it should be understood that these examples are only for illustration and should not be construed as limitations on the implementation of the present invention.

[0073] <Example>

[0074] General experimental materials:

[0075] 1. Source and culture of cancer cells:

[0076] The types and sources of cancer cells used in the following examples are shown in Table 1 below.

[0077] Table 1. Types and sources of cancer cells

[0078]

[0079] a: W.Hwang et al., (2017), Cancer Res., 1; 77(11):3013-3026

[0080] b: YW Chen et al., (2011), Mol. Biosyst., 7(11):3065-74

[0081] These cancer cells were cultured in RPMI 1640 medium [supplemented with 10% fetal bovine serum (FBS) (Corning) and 1X penicillin-streptomycin-glutamine (Corning)] in an incubator set at 37° C. and 5% CO 2 .

[0082] 2. Preparation of banana extract:

[0083] The banana extract used in the following examples was prepared according to the extraction method described in TW I584814B.

[0084] 3. Anti-cancer drugs:

[0085] The anticancer drugs used in the following examples were all purchased from Sigma-Aldrich, and their species names and product numbers are shown in Table 2 below.

[0086] Table 2. Types and product numbers of anticancer drugs

[0087]

[0088] General experimental methods:

[0089] 1. Statistical analysis:

[0090] In the following examples, the experimental data obtained are expressed as "mean ± standard error (SE)". Whether the difference between the experimental data of each group is statistically significant is evaluated by Student's t-test in Excel software. If the analysis result obtained is p < 0.05, it means that there is statistical significance.

[0091] Example 1. Evaluation of the efficacy of banana extract in the treatment of pancreatic cancer

[0092] Experimental methods:

[0093] A. Using banana extract to treat primary pancreatic cancer cells

[0094] To evaluate the effect of banana extract on primary pancreatic cancer cells, PANC-1 cells were first divided into 4 groups, including 1 control group and 3 extract groups (i.e., extract groups 1 to 3). 3 The number of cells / well was cultured in a 96-well plate and cultured in an incubator (37°C, 5% CO2) for 24 hours. Then, the medium containing different amounts of banana extract was replaced in each group according to Table 3 below, and cultured in an incubator (37°C, 5% CO2) for 72 hours. Then, the medium was replaced in each group with fresh medium, and cultured in an incubator (37°C, 5% CO2) for 72 hours.

[0095] Table 3. Content of banana extracts in each group

[0096]

[0097] Afterwards, the SRB colorimetric assay was performed according to C. H. Liao et al., (2020) Mar. Drugs, 29; 18(8): 399 to measure the cell survival rate of each group. Specifically, the liquid in each well was removed and an appropriate amount of SRB solution (Sigma-Aldrich, catalog number 230162) was added, and then the absorbance value (OD) of each well was read at a wavelength of 570 nm using a spectrophotometer. 570 The cell survival rate (%) of each group was calculated by dividing the measured absorbance value (OD 570 ) is substituted into the following formula (1) and calculated:

[0098] Formula (1): A = B / C

[0099] Where: A = cell survival rate (%)

[0100] B = OD measured in each group 570 Absorbance

[0101] C = OD measured in the control group 570 Absorbance

[0102] Afterwards, the obtained experimental data were analyzed according to the method described in item 1 of the above “General Experimental Methods”.

[0103] B. Using banana extract to treat drug-resistant pancreatic cancer cells

[0104] To evaluate the effect of banana extract on drug-resistant pancreatic cancer cells and their Gemcitabine sensitivity, PANC-1 / Gem cells were divided into 8 groups, including 1 control group, 3 extract groups (i.e., extract groups 1 to 3), 1 anticancer drug group, and 3 combination groups (i.e., combination groups 1 to 3). 3 The number of cells / well was cultured in a 96-well culture plate and cultured in an incubator (37° C., 5% CO2) for 24 hours. Then, the medium containing banana extract at different contents was replaced in each group according to Table 4 below, and cultured in an incubator (37° C., 5% CO2) for 72 hours. Then, the medium containing Gemcitabine at different contents was replaced in each group according to Table 4 below, and cultured in an incubator (37° C., 5% CO2) for 72 hours.

[0105] Table 4. Banana extract and Gemcitabine content in each group

[0106]

[0107] Then, the cell viability (%) was measured and statistically analyzed according to the method described in item A above.

[0108] In addition, in order to evaluate the effect of banana extract on Oxaliplatin sensitivity and 5-FU sensitivity of drug-resistant pancreatic cancer cells, the experiment was generally carried out according to the above method, except that 20 μM Gemcitabine was replaced by 1 μM Oxaliplatin and 2 μM 5-FU, respectively.

[0109] result:

[0110] Figure 1 Shows the effect of banana extract on the survival rate of PANC-1 cells in each group. Figure 1 It can be seen that there is no statistical difference in the cell survival rate between each extract group and the control group, which means that banana extract cannot inhibit the growth of PANC-1 cells.

[0111] Figures 2 to 4 The effects of banana extract on the survival rate of PANC-1 / Gem cells treated with Gemcitabine, Oxaliplatin and 5-FU are shown respectively. Figures 2 to 4 It can be seen that there is no statistical difference in the cell survival rate between each extract group and anticancer drug group and the corresponding control group, which means that the banana extract and the above three anticancer drugs cannot inhibit the growth of PANC-1 / Gem cells. However, the cell survival rate of each combination group is significantly lower than that of the corresponding control group, extract group and anticancer drug group, and the reduction rate increases with the increase of the content of the treated banana extract, which means that the banana extract can synergistically inhibit the growth of PANC-1 / Gem cells when used in combination with Gemcitabine, Oxaliplatin and 5-FU, and the banana extract can increase the sensitivity of PANC-1 / Gem cells to Gemcitabine, Oxaliplatin and 5-FU in a dose-dependent manner.

[0112] These experimental results show that banana extract itself cannot directly inhibit the growth of pancreatic cancer cells, but it can unexpectedly increase the sensitivity of pancreatic cancer anti-cancer drugs, that is, reduce drug resistance.

[0113] Example 2. Evaluation of the efficacy of banana extract in treating lung adenocarcinoma

[0114] Experimental methods:

[0115] A. Using banana extract to treat primary lung adenocarcinoma cells

[0116] To evaluate the effect of banana extract on primary lung adenocarcinoma cells, the experiment was conducted substantially as described in Example 1, Item A, except that PANC-1 cells were replaced with HCC827 cells.

[0117] B. Using banana extract to treat drug-resistant lung adenocarcinoma cells

[0118] In order to evaluate the effect of banana extract on drug-resistant lung adenocarcinoma cells and their Gefitinib sensitivity, the experiment was carried out generally according to the method described in Example 1, item B, except that PANC-1 / Gem cells were replaced with HCC827GR cells, and the treated 20 μM Gemcitabine was replaced with 1 μM Gefitinib.

[0119] result:

[0120] Figure 5 Shows the effect of banana extract on the survival rate of HCC827 cells in each group. Figure 5 It can be seen that there is no statistical difference in the cell survival rate between each extract group and the control group, which means that banana extract cannot inhibit the growth of HCC827 cells.

[0121] Figure 6 Shows the effect of banana extract on the survival rate of HCC827GR cells in each group treated with Gefitinib. Figure 6 It can be seen that there is no statistical difference in the cell survival rate between each extract group and the anticancer drug group and the control group, which means that neither banana extract nor Gefitinib can inhibit the growth of HCC827GR cells. However, the cell survival rate of each combination group is significantly lower than that of the corresponding control group, extract group and anticancer drug group, and the reduction rate increases with the increase of the content of the treated banana extract, which means that banana extract can synergistically inhibit the growth of HCC827GR cells when used in combination with Gefitinib, and banana extract can increase the sensitivity of HCC827GR cells to Gefitinib in a dose-dependent manner.

[0122] These experimental results show that banana extract itself cannot directly inhibit the growth of lung adenocarcinoma cells, but it can unexpectedly increase the sensitivity of lung adenocarcinoma anticancer drugs, that is, reduce drug resistance.

[0123] Based on the above experimental results, the applicant believes that banana extract can be used in the treatment of various cancers to increase the sensitivity of anticancer drugs (including chemotherapy drugs and targeted drugs) or reduce drug resistance.

[0124] All patents and literature references cited in this specification are hereby incorporated by reference in their entirety. In case of conflict, the present specification, including definitions, will control.

[0125] Although the present invention has been described with reference to the above specific embodiments, it is apparent that many modifications and variations can be made without departing from the scope and spirit of the invention. It is therefore intended that the present invention be limited only as indicated in the appended claims.

Claims

1. A use of a banana extract for preparing a pharmaceutical product for increasing the sensitivity of cancer cells to anticancer drugs, characterized in that: The banana extract is prepared by a method comprising the following steps: Prepare raw materials, which include banana (Musa paradisiaca) stems, leaves, barks or a combination thereof, and crush the raw materials into extracts to be extracted; The extract is immersed in a saline solution with a volume percentage of 5% to 40%, and heated, wherein the volume ratio of the extract to the saline solution is 95:5 to 60:40; Extracting the soaked extract by a low-temperature cell wall breaking method to obtain a crude extract, wherein the crude extract contains fiber and liquid; Centrifuging the crude extract to separate the fibers from the liquid in the crude extract, filtering the liquid portion and allowing it to stand in a bucket to obtain a crude extract; and The crude extract is fermented with far infrared ray stone to obtain banana extract.

2. The use according to claim 1, characterized in that: The cancer cells are drug-resistant cancer cells.

3. The use according to claim 1, characterized in that: The cancer cell is selected from the group consisting of pancreatic cancer cells, lung adenocarcinoma cells, and combinations thereof.

4. A combination for preparing a pharmaceutical for treating drug-resistant cancer, the combination comprising an anticancer drug or a pharmaceutically acceptable salt thereof, and a banana extract, characterized in that: The banana extract is prepared by a method comprising the following steps: Prepare raw materials, which include banana stems, leaves, barks or a combination thereof, and crush the raw materials into extracts to be extracted; The extract is immersed in a saline solution with a volume percentage of 5% to 40%, and heated, wherein the volume ratio of the extract to the saline solution is 95:5 to 60:40; Extracting the soaked extract by a low-temperature cell wall breaking method to obtain a crude extract, wherein the crude extract contains fiber and liquid; Centrifuging the crude extract to separate the fibers from the liquid in the crude extract, filtering the liquid portion and allowing it to stand in a bucket to obtain a crude extract; and The crude extract is fermented with far infrared ray stone to obtain banana extract.

5. The use according to claim 4, characterized in that: The cancer is selected from the group consisting of pancreatic cancer, lung adenocarcinoma, and combinations thereof.

6. The use according to claim 4, characterized in that: The banana extract and the anticancer drug are in a single dosage form or separate dosage forms.

7. The use according to claim 4, characterized in that: The banana extract is in a dosage form for parenteral administration, oral administration or topical administration.

8. The use according to claim 4, characterized in that: The anticancer drug is in a dosage form for parenteral administration, oral administration or topical administration.

9. The use according to claim 1 or 4, characterized in that: The anticancer drug is selected from the group consisting of Gefitinib, Gemcitabine, Oxaliplatin, 5-FU, and a combination thereof.

10. The use according to claim 1 or 4, characterized in that: In the step of preparing the raw materials, the weight ratio of the stem, leaves and bark is 5:3:2 to 6:2:

2.

11. The use according to claim 1 or 4, characterized in that: In the step of soaking the extract in saline solution with a volume percentage of 5% to 40% and heating the extract, the volume ratio of the extract to the saline solution is 70:

30.

12. The use according to claim 1 or 4, characterized in that: In the step of centrifuging the crude extract, the crude extract was centrifuged at 3000 rpm (RCF) for 1 minute.

13. The use according to claim 1 or 4, characterized in that: In the step of centrifuging the crude extract and letting the liquid after filtering the liquid part stand in a barrel, the crude extract is 80% to 90% of the upper liquid in the barrel.

14. The use according to claim 1 or 4, characterized in that: The banana extract is liquid, dark golden brown in color, with a specific gravity of 1.12±10%, a viscosity of 1.914±10 centistokes, a boiling point of 104±10°C and a water solubility of 100%; among the chemical properties of the extract, the pH value is 13, the sodium content is 55,000±10% (mg / kg), the potassium content is 1192±10% (mg / kg), the calcium content is 33±10% (mg / kg), the magnesium content is 26±10% (mg / kg), the zinc content is 9±10% (mg / kg) and the iron content is 9±10% (mg / kg).

Images