Application of marigold glycosides in the treatment of esophageal squamous cell carcinoma

Abstract

The present invention provides an application of marigold glycosides for treating esophageal squamous cell carcinoma. The present invention finds that the tyrosine 174, 302, and 328 sites of fructose bisphosphate aldolase (ALDOA) ​​are highly expressed in esophageal squamous cell carcinoma tissues and are negatively correlated with the prognosis of esophageal squamous cell carcinoma patients; marigold glycosides can play an anti-esophageal squamous cell carcinoma effect, and can dose-dependently inhibit the activation of the phosphorylation sites of ALDOA tyrosine 174, 302, and 328 in esophageal squamous cell carcinoma cells. Therefore, marigold glycosides are an effective anti-esophageal squamous cell carcinoma drug.

Description

Technical Field

[0001] The present invention relates to the field of medicine, and in particular to the application of marigold glycoside in treating esophageal squamous cell carcinoma. Background Art

[0002] From the perspective of pathological type, esophageal cancer is divided into esophageal squamous cell carcinoma and esophageal adenocarcinoma. Among them, esophageal squamous cell carcinoma (ESCC) is one of the common solid tumors that is endemic and highly prevalent in China, and there are few related studies abroad. There are many inducing factors for esophageal squamous cell carcinoma, which are mainly related to drinking, smoking, and various chronic irritations that cause damage to the esophagus. At present, in clinical practice, ESCC lacks specific and effective drugs and treatment options. As a result, esophageal squamous cell carcinoma is prone to metastasis and recurrence, and the 5-year survival rate is extremely low. Therefore, finding effective therapeutic targets and options, and clarifying the relevant molecular mechanisms are of great significance for the diagnosis and treatment of ESCC.

[0003] Tyrosine kinase inhibitors are the most important small molecule targeted anticancer drugs. Small molecule compounds targeting tyrosine kinases, such as gefitinib, have been clinically used in a variety of tumors. However, the expression profile of tyrosine kinases in ESCC is still unclear. Some studies have now found that some metabolites can promote tumor progression after phosphorylation activation. However, whether tyrosine phosphorylation of metabolites can be used as a target for the diagnosis and treatment of ESCC remains to be explored in depth.

[0004] Quercetagitrin is obtained from African marigold and has the following structural formula:

[0005]

[0006] Marigold glycosides have anti-inflammatory and antioxidant biological activities and are widely used in cardiovascular and cerebrovascular diseases and other diseases related to inflammation and oxidation. In recent years, it has also been reported that marigold glycosides have anti-cancer effects by inhibiting the growth of tumor cells. However, it remains unknown whether marigold glycosides can be used as a lead compound for targeted drugs and play a role in fighting esophageal squamous cell carcinoma. Summary of the invention

[0007] The present invention finds that marigold glycoside has an outstanding effect against esophageal squamous cell carcinoma and can be used to prepare a drug for preventing or treating esophageal squamous cell carcinoma, thereby proposing the present invention.

[0008] The present invention found that the tyrosine 174, 302, and 328 sites of human fructose bisphosphate aldolase (ALDOA) ​​are highly expressed in esophageal squamous cell carcinoma tissues, and are negatively correlated with the prognosis of patients with esophageal squamous cell carcinoma, suggesting that the tyrosine 174, 302, and 328 sites of ALDOA are important marker molecules for targeting the progression of esophageal squamous cell carcinoma. Quercetagitrin can prevent esophageal squamous cell carcinoma. Cell experiment results show that quercetagitrin can dose-dependently inhibit the growth (MTS method) and invasion (Transwell method) of esophageal squamous cell carcinoma cell line KYSE510. It was found by immunoblotting that quercetagitrin can dose-dependently inhibit the activation of phosphorylation sites of ALDOA tyrosine 174, 302, and 328 in KYSE410 and KYSE510 cells. Importantly, after nonsense mutation of ALDOA tyrosine 174, 302, and 328 to alanine, marigold glycosides could no longer mediate their anti-esophageal squamous cell carcinoma cell growth and invasion effects. Animal experiments showed that marigold glycosides could effectively inhibit the metastasis of tumor cells in the KYSE410 and KYSE510 lymphatic metastasis mouse models, and could not further enhance the lymphatic metastasis of tumor cells in mice injected with AAV8 virus-coated ALDOA tyrosine 174, 302, and 328 nonsense mutation vectors. These results all confirm that marigold glycosides can play an anti-esophageal squamous cell carcinoma effect by blocking the activation of ALDOA tyrosine 174, 302, and 328 sites.

[0009] Therefore, in the first aspect, the present invention provides a use of marigold glycoside or a pharmaceutically acceptable salt, prodrug, or metabolite thereof in the preparation of a medicament for preventing or treating esophageal squamous cell carcinoma.

[0010] In a preferred embodiment, the prevention or treatment of esophageal squamous cell carcinoma is achieved by blocking the activation of at least one of the tyrosine 174, 302, and 328 sites of fructose bisphosphate aldolase (ALDOA).

[0011] In a second aspect, the present invention provides a use of marigold glycoside or a pharmaceutically acceptable salt, prodrug, or metabolite thereof in the preparation of a drug for inhibiting the activation of at least one of tyrosine 174, 302, and 328 sites of fructose bisphosphate aldolase (ALDOA).

[0012] In a third aspect, the present invention provides a use of marigold glycoside or a pharmaceutically acceptable salt, prodrug, or metabolite thereof in the preparation of a method for preventing or treating a disease mediated by at least one of the tyrosine 174, 302, and 328 sites of fructose bisphosphate aldolase (ALDOA).

[0013] In a preferred embodiment, the disease comprises esophageal squamous cell carcinoma.

[0014] In a fourth aspect, the present invention provides a use of an activation blocker of at least one of the tyrosine 174, 302, and 328 sites of fructose bisphosphate aldolase (ALDOA) ​​in the preparation of a drug for preventing or treating esophageal squamous cell carcinoma.

[0015] In a preferred embodiment, the activation blocker of at least one of the tyrosine 174, 302, and 328 sites of fructose bisphosphate aldolase (ALDOA) ​​comprises tagetoid glycoside or a pharmaceutically acceptable salt, prodrug, or metabolite thereof.

[0016] Preferably, in the present invention, the fructose bisphosphate aldolase is human fructose bisphosphate aldolase.

[0017] Preferably, in the present invention, the activation of fructose bisphosphate aldolase refers to the phosphorylation of fructose bisphosphate aldolase.

[0018] Preferably, in the present invention, the prevention or treatment of esophageal squamous cell carcinoma includes at least one of inhibiting the growth of esophageal squamous cell carcinoma cells, inhibiting the invasion of esophageal squamous cell carcinoma cells, and inducing apoptosis of esophageal squamous cell carcinoma cells, and more preferably includes inhibiting the growth of esophageal squamous cell carcinoma cells and inhibiting the invasion of esophageal squamous cell carcinoma cells.

[0019] Also preferably, the esophageal squamous cell carcinoma cells include esophageal squamous cell carcinoma cell line KYSE410, esophageal squamous cell carcinoma cell line KYSE450, esophageal squamous cell carcinoma cell line KYSE510, and esophageal squamous cell carcinoma cell line KYSE30, and more preferably esophageal squamous cell carcinoma cell line KYSE410, esophageal squamous cell carcinoma cell line KYSE510, and esophageal squamous cell carcinoma cell line KYSE30.

[0020] In the present invention, the pharmaceutically acceptable salt of tagetoid glycoside includes a salt formed by tagetoid glycoside and a pharmaceutically acceptable acid or base.

[0021] In the present invention, the prodrug refers to a derivative that can directly or indirectly provide tagetoid glycoside after being administered to a patient, such as an ester of tagetoid glycoside.

[0022] In the present invention, the metabolite refers to a pharmaceutically acceptable metabolic derivative form of marigold glycoside or a pharmaceutically acceptable salt thereof.

[0023] Preferably, the medicine of the present invention further comprises a pharmaceutically acceptable adjuvant.

[0024] As pharmaceutically acceptable adjuvants, any adjuvant known to be suitable for preparing a specific drug can be used. Examples include, but are not limited to, solvents, excipients, dispersants, emulsifiers, solubilizers, gel formers, ointment bases, antioxidants, preservatives, stabilizers, carriers, fillers, bonding agents, thickeners, complexing agents, disintegrants, buffers, penetration enhancers, polymerizers, lubricants, coating agents, propellants, tonicity regulators, surfactants, colorants, flavoring agents, sweeteners and dyes. Particularly adjuvants of the type suitable for the desired formulation and the desired mode of administration are used.

[0025] The medicine of the present invention can be one of tablets, powders, granules, pills, capsules, solutions, eye drops, emulsions, suspensions, ointments, oils, pastes, foams, sprays, injections, skin patches, suppositories, liposome preparations, microparticle preparations, and microcapsule preparations.

[0026] The medicaments of the present invention are suitable for oral, rectal, nasal, topical (including transdermal, buccal and sublingual), vaginal, parenteral (including subcutaneous, intramuscular, intravenous and intradermal) or pulmonary administration.

[0027] The medicament of the present invention can be produced in a manner known to those skilled in the art, for example, by dissolving, mixing, granulating, sugar-coating, levigating, emulsifying, encapsulating, entrapping or lyophilizing processes.

[0028] In the medicine of the present invention, the amount of marigold glycoside or its pharmaceutically acceptable salt, prodrug, metabolite can account for 0.01% to 50% of the total weight, preferably 0.1% to 10%, more preferably 0.5% to 5%, most preferably 1% to 2%.

[0029] The therapeutic amount can be determined empirically and will vary with the pathology being treated, the weight of the subject being treated, and the efficacy and toxicity of the agent. Similarly, those skilled in the art can easily determine the appropriate dosage formulation and method of administering the agent. For example, for adult patients, the marigold glycoside or its pharmaceutically acceptable salt, prodrug, metabolite of the present invention can be administered orally or parenterally in a daily dosage of 0.001 mg to 500 mg, once a day or divided into several times. BRIEF DESCRIPTION OF THE DRAWINGS Description of the drawings:

[0031] Figure 1 ALDOA tyrosine 174, 302, 328 of Example 1 is highly expressed in esophageal squamous cell carcinoma tissue and lowly expressed in adjacent tissues. ALDOA tyrosine 174, 302, 328 highly expressed in esophageal squamous cell carcinoma tissue is positively correlated with esophageal squamous cell carcinoma lymph node metastasis and negatively correlated with esophageal squamous cell carcinoma patient survival time.

[0032] Figure 2This is a schematic diagram of the results of Example 2 showing that marigold glycosides inhibit the proliferation and invasion of the esophageal squamous cell carcinoma cell line KYSE510 in a dose-dependent manner.

[0033] Figure 3 Schematic diagram of the results of marigold glycosides in Example 3 dose-dependently inhibiting ALDOA tyrosine phosphorylation activation, ALDOA enzyme activity and product (G3P) production in in situ and metastatic KYSE410 and KYSE510 esophageal squamous cell carcinoma cells.

[0034] Figure 4 This is a schematic diagram of the results showing that marigold glycosides and ALDOA tyrosine 174A nonsense mutation, 302A nonsense mutation and 328A nonsense mutation can inhibit the growth and invasion of esophageal squamous cell carcinoma cells in situ and metastatic foci. Importantly, after marigold glycosides were combined with these nonsense mutations, the ability of marigold glycosides to resist the progression of esophageal squamous cell carcinoma cells was not further enhanced, indicating that ALDOA tyrosine 174, 302 and 328 sites are molecular targets for marigold glycosides to resist the progression of esophageal squamous cell carcinoma.

[0035] Figure 5 The marigold glycoside and AAV8-ALDOAY174 / 302 / 328A of Example 5 can both inhibit the lymphatic metastasis of esophageal squamous cell carcinoma cell lines KYSE410 and KYSE510 and the expression of Ki67 and LYVE1 in carcinoma in situ tissues. After marigold glycoside combined with AAV8-ALDOA Y174 / 302 / 328A, its anti-cancer effect was not significantly improved. The anti-esophageal squamous cell carcinoma effect of marigold glycoside was further confirmed in the animal model and the results of determining that ALDOA tyrosine 174, 302 and 328 sites are molecular targets for marigold glycoside to exert anti-esophageal squamous cell carcinoma progression are schematic diagrams.

[0036] Figure 6 This is a schematic diagram showing the results that marigold glycoside (Quer) in Example 6 is more effective than quercetin in inhibiting the invasion of esophageal squamous cell carcinoma cell line KYSE30.

[0037] In the above figures, * represents P < 0.05; ** represents P < 0.01; *** represents P < 0.001; ns represents no statistical difference. DETAILED DESCRIPTION

[0038] The preferred embodiments of the invention are described in detail below. The examples are provided to better illustrate the content of the invention, but the content of the invention is not limited to the examples. Non-essential improvements and adjustments to the implementation scheme according to the content of the invention still fall within the scope of the invention.

[0039] The experimental methods in the following examples are all conventional methods unless otherwise specified. If no specific techniques or conditions are specified in the examples, they are carried out according to the techniques or conditions described in the literature in the art or according to the product instructions.

[0040] Example 1: ALDOA tyrosine 174, 302, and 328 are highly expressed in local esophageal squamous cell carcinoma and are closely related to ESCC progression

[0041] 1. Immunohistochemistry

[0042] Pathological sections of 10 paracancerous tissues and 55 esophageal squamous cell carcinoma tissues were routinely dewaxed and antigen repaired, and then incubated with ALDOA tyrosine 174, 302, and 328 antibodies for color development. The expression intensity of the three ALDOA tyrosine antibodies in local tissues was observed by immunohistochemistry.

[0043] 2. Immunohistochemical results scoring to determine the expression of ALDOA tyrosine 174, 302, and 328 in esophageal squamous cell carcinoma tissues and adjacent esophageal tissues

[0044] The immunohistochemical results are calculated based on the staining intensity (the staining intensity is divided into four levels: 0, 1, 2, and 3) multiplied by the proportion of positive cells in the local tissue (the staining area is divided into five levels: 0, 1, 2, 3, and 4). If the product is greater than 3, it is high expression (positive), and if it is less than or equal to 3, it is low expression (negative).

[0045] 3. Correlation between ALDOA tyrosine 174, 302, 328 and lymph node metastasis and survival time in patients with esophageal squamous cell carcinoma based on immunohistochemical results

[0046] The local tissues of 55 patients with esophageal squamous cell carcinoma were divided into metastatic group and non-metastatic group according to the presence of lymphatic metastasis. The chi-square test was used to determine the correlation between ALDOA tyrosine 174, 302, and 328 and esophageal squamous cell carcinoma metastasis. The survival curve was used to analyze whether high-expression and low-expression ALDOA tyrosine 174, 302, and 328 could be used as markers to determine the survival time of patients with esophageal squamous cell carcinoma.

[0047] Compare with Figure 1 ALDOA tyrosine 174, 302, and 328 were highly expressed in esophageal squamous cell carcinoma tissues and lowly expressed in adjacent tissues. Highly expressed ALDOA tyrosine 174, 302, and 328 in esophageal squamous cell carcinoma tissues were positively correlated with esophageal squamous cell carcinoma lymph node metastasis and negatively correlated with the survival time of esophageal squamous cell carcinoma patients.

[0048] Example 2: Marigold glycoside inhibits the growth and invasion of esophageal squamous cell carcinoma cell line KYSE510

[0049] 1. Cell Proliferation Assay

[0050] KYSE510 cells were cultured at 3 × 10 3 The cells were inoculated at a density of 100 cells / well in a 96-well plate, and marigold glycoside (concentrations: 1, 2.5, 5, 10, 25, 50, 100 μM) was added after the cells adhered to the wall. After 72 hours, 10% MTS solution was prepared with RPMI 1640 medium, the cultured cells were taken out, the upper medium was discarded, and the prepared MTS was added and incubated for 2 hours, and the absorbance value was measured at 490 nm by an ELISA reader.

[0051] 2. Cell invasion ability detection

[0052] The KYSE510 cell line was cultured in serum-free medium for 24 hours. Using a transwell chamber with an 8 μm pore size, 100 μL of matrix gel was added to the upper chamber of the chamber and incubated at 37°C for 1 hour to solidify the matrix gel. The prepared KYSE510 cell line was inoculated in the upper chamber of the transwell chamber, and 800 μL of RPMI 1640 medium containing 20% ​​fetal bovine serum was added to the lower chamber, and marigold glycoside (concentration: 10, 25, 50 μM) was added. The transwell chamber was placed in an incubator and incubated for 24 hours. After taking it out, the inner wall of the upper chamber was wiped clean with a cotton swab, and the invading cells in the lower chamber were separated by dissociation solution and then cell dye was added, and the invasion cell rate was calculated by an ELISA instrument.

[0053] Compare with Figure 2 , marigold glycosides inhibited the proliferation and invasion of esophageal squamous cell carcinoma cell line KYSE510 in a dose-dependent manner.

[0054] Example 3: Tagetes erecta glycosides inhibit ALDOA tyrosine phosphorylation activation, ALDOA enzyme activity and product production in esophageal squamous cell carcinoma cells in situ and metastatic lesions

[0055] 1. Marigold glycosides inhibit the phosphorylation of ALDOA tyrosine 174, 302, and 328 in esophageal squamous cell carcinoma cells in situ and metastasis

[0056] After KYSE410 and KYSE510 cells were inoculated into the footpads of nude mice (4-week-old female BALB / c-nu nude mice (average weight 14-15 grams), purchased from Vital River Company), the in situ tumor tissue and popliteal metastatic lymph nodes were obtained, and then ground into cell suspensions. The in situ and metastatic KYSE410 and KYSE510 esophageal squamous cell carcinoma cells were obtained by CD326 magnetic bead sorting. The cultured in situ and metastatic KYSE410 and KYSE510 esophageal squamous cell carcinoma cells were incubated with marigold glycosides (concentrations: 10 and 25 μM) for 24 hours, and then the cells were collected. RIPA lysis buffer was added and lysed on ice for 1 hour, with shaking every 10 minutes. After lysis, the supernatant was collected after centrifugation at 4°C, 12000 rpm, and 20 minutes to obtain protein lysate. The expression of ALDOA and ALDOA tyrosine 174, 302, and 328 in the cells was observed by immunoblotting.

[0057] 2. Marigold glycosides inhibit ALDOA activity in esophageal squamous cell carcinoma cells in situ and metastatic lesions

[0058] After incubating the cultured in situ and metastatic KYSE410 and KYSE510 esophageal squamous cell carcinoma cells with marigold glycosides (concentrations: 10 and 25 μM) for 24 hours, the cells were collected. The collected cells were incubated in ALDOA activity assay buffer at 4°C for 20 minutes. After centrifugation at 12000 rpm for 5 minutes, the supernatant was collected and placed in a system containing ALDOA activity buffer substrate, etc., and the absorbance value was measured by an ELISA reader at 450nm.

[0059] 3. Marigold glycosides inhibit the production of glyceraldehyde-3-phosphate (G3P) in esophageal squamous cell carcinoma cells in situ and metastasis

[0060] After incubating the cultured in situ and metastatic KYSE410 and KYSE510 esophageal squamous cell carcinoma cells with marigold glycosides (concentrations: 10 and 25 μM) for 24 hours, the cells were collected. After the collected cells were incubated in 100 μL pre-cooled G3P assay buffer for 30 minutes, the supernatant was collected by centrifugation and placed in 50 μL G3P assay buffer, and the G3P content was detected in a microplate reader with an excitation and emission wavelength of 535 / 587 nm.

[0061] Compare with Figure 3 The results showed that marigold glycosides dose-dependently inhibited ALDOA tyrosine phosphorylation activation, ALDOA enzyme activity and product (G3P) production in situ and metastatic KYSE410 and KYSE510 esophageal squamous cell carcinoma cells.

[0062] Example 4: ALDOA tyrosine 174, 302, 328 sites are molecules that marigold glycosides inhibit the progression of esophageal squamous cell carcinoma

[0063] 1. Cell Proliferation Assay

[0064] KYSE410 and KYSE510 esophageal squamous cell carcinoma cells in situ and metastatic foci containing blank vector, ALDOA tyrosine 174A nonsense mutation, 302A nonsense mutation, and 328A nonsense mutation plasmids were cultured at 3×10 3 The cells were inoculated at a density of 100 cells / well in a 96-well plate, and marigold glycoside (25 μM) was added after the cells adhered to the wall. After 72 hours, 10% MTS solution was prepared with RPMI 1640 medium, the cultured cells were taken out, the upper medium was discarded, and the prepared MTS was added and incubated for 2 hours. The absorbance value was measured at 490 nm by an ELISA reader.

[0065] 2. Cell invasion ability detection

[0066] KYSE410 and KYSE510 esophageal squamous cell carcinoma cells in situ and metastatic foci containing blank vector, ALDOA tyrosine 174A nonsense mutation, 302A nonsense mutation, and 328A nonsense mutation plasmids were cultured in serum-free medium for 24 hours. Using a transwell chamber with an 8 μm pore size, 100 μL of matrigel was added to the upper chamber of the chamber and incubated at 37°C for 1 hour to solidify the matrigel. The prepared cells were inoculated in the upper chamber of the transwell chamber, 800 μL of RPMI 1640 medium containing 20% ​​fetal bovine serum was added to the lower chamber, and marigold glycoside (25 μM) was added. The transwell chamber was placed in an incubator and incubated for 24 hours. After removal, the inner wall of the upper chamber was wiped clean with a cotton swab, and the invasive cells in the lower chamber were separated by dissociation solution and then added with cell dye, and the invasion cell rate was calculated by an ELISA instrument.

[0067] Compare with Figure 4 The results showed that marigold glycosides and ALDOA tyrosine 174A nonsense mutation, 302A nonsense mutation and 328A nonsense mutation can inhibit the growth and invasion of esophageal squamous cell carcinoma cells in situ and metastatic lesions. Importantly, after marigold glycosides were combined with these nonsense mutations, the anti-progression ability of marigold glycosides in esophageal squamous cell carcinoma cells was not further enhanced, suggesting that ALDOA tyrosine 174, 302 and 328 sites are the molecular targets of marigold glycosides to exert anti-progression of esophageal squamous cell carcinoma.

[0068] Example 5: In esophageal squamous cell carcinoma cell lines KYSE450 and KYSE510 tumor-bearing mice, marigold glycoside inhibits the ALDOA tyrosine site to exert anti-tumor effects

[0069] After inoculating KYSE410 and KYSE510 cells into the footpads of nude mice (4-week-old female BALB / c-nu nude mice (average weight 14-15 g), purchased from Vital River), about one week later, ALDOAY174 / 302 / 328A (1×1011 vg injection per mouse) coated with AAV8 virus was injected into the in situ carcinoma tissue of the mouse footpads, and marigold glycosides (25 mg / kg / day) were administered orally. The experiment lasted for 5 weeks. The popliteal lymph nodes were collected, and the volume was calculated as follows: Volume = Long diameter × Transverse diameter 2 ×0.5. The size of the metastatic lymphatic channel was observed by HE staining. The carcinoma in situ tissue was collected, and the protein lysate in the carcinoma in situ tissue was collected by lysate. The expression of the proliferation marker Ki67 and the lymphangiogenesis marker LYVE1 in the local tumor tissue was further observed by high-throughput enzyme-linked immunosorbent assay (ELISA).

[0070] Compare with Figure 5 The results showed that marigold glycosides and AAV8-ALDOAY174 / 302 / 328A can inhibit the lymphatic metastasis of esophageal squamous cell carcinoma cell lines KYSE410 and KYSE510 and the expression of Ki67 and LYVE1 in carcinoma in situ tissues. The anti-cancer effect of marigold glycosides was not significantly improved after combining with AAV8-ALDOAY174 / 302 / 328A. The anti-esophageal squamous cell carcinoma effect of marigold glycosides was further confirmed in animal models, and the ALDOA tyrosine 174, 302 and 328 sites were determined to be the molecular targets of marigold glycosides in the anti-esophageal squamous cell carcinoma progression.

[0071] Example 6: Marigold glycosides are more effective than quercetin in inhibiting the invasion of esophageal squamous cell carcinoma cells

[0072] Cell invasion ability assay

[0073] The KYSE30 cell line was cultured in serum-free medium for 24 hours. Using a transwell with an 8 μm pore size, 100 μL of matrix gel was added to the upper chamber of the chamber and incubated at 37°C for 1 hour to solidify the matrix gel. The prepared KYSE30 cell line was inoculated in the upper chamber of the transwell, and 800 μL of RPMI 1640 medium containing 20% ​​fetal bovine serum was added to the lower chamber, and marigold glycosides or quercetin (concentration of 25 μM) were added. The transwell was placed in an incubator and incubated for 24 hours. After removal, the inner wall of the upper chamber was wiped clean with a cotton swab, and the invasive cells in the lower chamber were separated by dissociation solution and then cell dye was added, and the invasion cell rate was calculated by an ELISA instrument.

[0074] Compare with Figure 6The results showed that marigold glycosides were more effective than quercetin in inhibiting the invasion of esophageal squamous cell carcinoma cell line KYSE30

[0075] Embodiment 7:

[0076] The liposome-encapsulated marigold glycoside is prepared as a drug for treating esophageal squamous cell carcinoma.

[0077] Embodiment 8:

[0078] Add marigold glycoside to excipients according to the required proportion of the preparation to prepare tablets.

[0079] Embodiment 9:

[0080] Add marigold glycoside to excipients according to the required proportion of the preparation to prepare powder.

[0081] Embodiment 10:

[0082] The marigold glycoside extract is spray-granulated, dried, and granulated to obtain granules, which are used as medicines and health products for preventing and treating esophageal squamous cell carcinoma.

[0083] Embodiment 11:

[0084] The marigold glycoside is dissolved in water, finely filtered, sealed and sterilized to prepare an injection.

[0085] Finally, it should be noted that the above preferred embodiments are only used to illustrate the technical solutions of the present invention rather than to limit it. Although the present invention has been described in detail through the above preferred embodiments, those skilled in the art should understand that various changes can be made in form and details without departing from the scope defined by the claims of the present invention.

Claims

1. Use of marigold glycoside or a pharmaceutically acceptable salt thereof in the preparation of a medicament for preventing or treating esophageal squamous cell carcinoma.

2. The use according to claim 1, characterized in that: The prevention or treatment of esophageal squamous cell carcinoma is achieved by blocking the activation of at least one of the tyrosine 174, 302, and 328 sites of fructose bisphosphate aldolase.

3. The use according to claim 1 or 2, characterized in that: The prevention or treatment of esophageal squamous cell carcinoma comprises at least one of inhibiting the growth of esophageal squamous cell carcinoma cells, inhibiting the invasion of esophageal squamous cell carcinoma cells, and inducing apoptosis of esophageal squamous cell carcinoma cells.

4. The use according to claim 3, characterized in that: The esophageal squamous cell carcinoma cells include esophageal squamous cell carcinoma cell line KYSE410, esophageal squamous cell carcinoma cell line KYSE450, esophageal squamous cell carcinoma cell line KYSE510, and esophageal squamous cell carcinoma cell line KYSE30.

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