Medicine for treating neuroendocrine tumor

Abstract

The invention belongs to the technical field of biological medicines, and relates to a medicine for treating neuroendocrine tumors. It is found for the first time that sanguinarine can significantly inhibit proliferation of neuroendocrine tumor cells (STC-1 and H460 cell lines) and promote apoptosis of the neuroendocrine tumor cells, so that the neuroendocrine tumor cells are retarded in a G0 / G1 phase or a G2 / M phase, and the clone formation ability of the neuroendocrine tumor cells is inhibited. Therefore, sanguinarine can be used for preparing drugs for preventing, relieving or / and treating neuroendocrine tumors, and a new idea is provided for treatment of neuroendocrine tumors.

Description

Technical Field

[0001] The present invention belongs to the field of biomedicine technology, and in particular relates to a drug for treating neuroendocrine tumors. Background Art

[0002] Neuroendocrine neoplasms (NENs) are a heterogeneous group of tumors with neuroendocrine differentiation and specific marker expression. They arise from peptidergic neurons and neuroendocrine cells distributed throughout various organ systems. Their anatomical distribution shows remarkable organ specificity, with gastroentero-pancreatic neuroendocrine neoplasms (GEP-NENs) arising from the lungs and digestive system being the most common, accounting for approximately 65%-75% of all NEN cases. Epidemiological data show a significant 6.4-fold increase in the global incidence of NENs over the past three decades, with GEP-NENs being the predominant subtype. Although they often exhibit an indolent growth pattern, clinical observations have demonstrated that approximately 40%-50% of cases have the potential for malignant transformation, with the liver being the most common target of distant metastases.

[0003] A multimodal comprehensive treatment system has been formed for the clinical treatment of this type of tumor, with the main technical means including: Drug treatment systems include biologics (such as interferon), molecularly targeted drugs (such as sunitinib), cytotoxic chemotherapy drugs (such as temozolomide), hormone modulators (such as lanreotide), and somatostatin analogs (such as octreotide). In recent years, the development of new drugs, represented by the multi-target tyrosine kinase inhibitor surufatinib, has provided new molecular targeted intervention options for the treatment of NETs.

[0004] Surgical treatment strategies include minimally invasive endoscopic resection (for localized lesions) and radical resection (for localized primary lesions). For liver metastases, established interventional treatment techniques include radiofrequency ablation, transcatheter arterial embolization, and iodine-125 seed implantation.

[0005] Combination therapy model: Through drug combination regimens (such as sorafenib combined with temozolomide) or interdisciplinary treatment combinations (such as targeted therapy combined with immune checkpoint inhibitors), a multi-dimensional synergistic treatment strategy is formed, which has shown synergistic effects in clinical studies.

[0006] However, the existing treatment technology system still has the following technical defects that need to be addressed: (1) Drug treatment: The objective response rate of existing monotherapy drugs is limited, and there is a general risk of drug resistance (for example, the median progression time of sunitinib treatment is only 11.4 months), accompanied by dose-limiting toxic reactions such as diarrhea and hypertension; (2) Limitations of surgical intervention: Radical surgery is only suitable for early localized lesions (accounting for less than 20%), and the control rate of interventional therapy for diffuse liver metastases is less than 45%; (3) Bottlenecks in combined therapy: There is a lack of standardized protocols for multimodal sequential therapy, and the mechanism of drug interaction has not been fully elucidated, resulting in significant individual differences in treatment response rates (ORR fluctuates between 15% and 60%). (4) Recurrence and metastasis prevention and control: Existing treatment methods are insufficient to eliminate tiny residual lesions. The recurrence and metastasis rate is still as high as 30%-50% 2 years after surgery, which significantly affects the long-term survival benefits of patients.

[0007] The above technical limitations highlight the clinical need to develop new anti-tumor drugs and innovative treatment methods, especially new intervention targets for key pathways of malignant progression of GEP-NENs, and combination drug regimens that can break through existing treatment bottlenecks. These have become important research directions for improving the clinical prognosis of this type of tumor. Summary of the Invention

[0008] In view of the problems and shortcomings in the prior art, the present invention aims to provide a drug for the treatment of neuroendocrine tumors.

[0009] A first aspect of the present invention provides the use of sanguinarine in preparing a product for preventing, alleviating or / and treating neuroendocrine tumors.

[0010] A second aspect of the present invention provides the use of sanguinarine in the preparation of a product for inhibiting the proliferation of neuroendocrine tumor cells.

[0011] A third aspect of the present invention provides the use of sanguinarine in the preparation of a product for promoting apoptosis of neuroendocrine tumor cells.

[0012] A fourth aspect of the present invention provides the use of sanguinarine in the preparation of a product for blocking the cell cycle of neuroendocrine tumors.

[0013] A fifth aspect of the present invention provides the use of sanguinarine in the preparation of a product for alleviating and / or treating inflammatory reactions caused by neuroendocrine tumors.

[0014] According to the above application, preferably, the neuroendocrine tumors in the present invention include gastrointestinal and pancreatic neuroendocrine tumors and large cell lung cancer.

[0015] A sixth aspect of the present invention provides a product for alleviating and / or treating neuroendocrine tumors, wherein the product contains sanguinarine and a neuroendocrine tumor therapeutic drug, wherein the neuroendocrine tumor therapeutic drug is a neuroendocrine tumor targeted therapeutic drug or a neuroendocrine tumor chemotherapy drug.

[0016] According to the above product, preferably, the neuroendocrine tumor targeted therapeutic drug is at least one of sunitinib, surufatinib, bevacizumab, and everolimus; According to the above product, preferably, the neuroendocrine tumor chemotherapy drug is at least one of temozolomide, cisplatin, etoposide, and streptozotocin.

[0017] According to the above product, preferably, the product further contains pharmaceutically acceptable excipients.

[0018] Compared with the prior art, the present invention has the following positive and beneficial effects: (1) The present invention first discovered that sanguinarine can directly act on neuroendocrine tumor cells, block the cell cycle, induce apoptosis of neuroendocrine tumor cells, and inhibit the proliferation and cloning of neuroendocrine tumor cells. Further research has found that sanguinarine can interfere with the signal transduction pathways of neuroendocrine tumor cells, thereby blocking their growth and spread. At the same time, sanguinarine can also affect the metabolic pathways of neuroendocrine tumor cells, reducing their viability, thereby achieving the purpose of inhibiting tumor growth. Therefore, sanguinarine can be used as an adjuvant treatment for neuroendocrine tumors, opening up a new treatment approach for neuroendocrine tumors and providing new treatment options for patients with neuroendocrine tumors.

[0019] (2) Sanguinarine can induce autophagy and oxidative stress in neuroendocrine tumor cells, further weakening the survival basis of neuroendocrine tumor cells and enhancing their anti-tumor effect.

[0020] (3) The present invention has found through research that sanguinarine has a significant anti-inflammatory effect, can reduce the inflammatory response in the microenvironment of neuroendocrine tumors, and inhibit the growth and metastasis of neuroendocrine tumors; moreover, sanguinarine can enhance the body's immune function, increase the activity of immune cells, and enhance the body's anti-tumor ability.

[0021] (4) Through research, the present invention has discovered that sanguinarine can be used in combination with existing anti-tumor drugs to exert a synergistic effect. For example, when used in combination with chemotherapy drugs, sanguinarine can enhance the sensitivity of tumor cells to drugs and improve the chemotherapy effect; when used in combination with targeted therapy drugs, it can inhibit tumor growth through different mechanisms and achieve better therapeutic effects.

[0022] (5) As a traditional Chinese medicine ingredient, sanguinarine has a long history of clinical application, and its safety has been widely verified. Compared with chemically synthesized drugs, sanguinarine has the advantages of low toxicity and fewer side effects, making it more suitable for long-term treatment. Moreover, due to its good safety and low incidence of side effects, patients show high tolerance during treatment, which helps improve patient compliance and ensure the smooth implementation of the treatment plan.

[0023] (6) Sanguinarine is a commonly used Chinese medicine ingredient with a wide range of sources, relatively low cost, and easy to obtain on the market. It is easy to use and patients can take it themselves under the guidance of a doctor, which improves the convenience of treatment. Moreover, it helps to reduce the economic burden of patients and improve the accessibility of drugs. BRIEF DESCRIPTION OF THE DRAWINGS

[0024] Figure 1 This is the CCK-8 test result of the effect of sanguinarine on the proliferation of neuroendocrine tumor cell line STC-1 (mouse small intestinal neuroendocrine cells); Figure 2 The figure shows the CCK-8 test results of the effect of sanguinarine on the proliferation of neuroendocrine tumor cell line H460 (human large cell lung cancer cells); Figure 3 Figures 2 and 3 show the effect of sanguinarine on apoptosis in the STC-1 cell line. A: apoptosis assay results for the blank control group of the STC-1 cell line; B: apoptosis assay results for the STC-1 cell line treated with 0.15 μM sanguinarine; C: apoptosis assay results for the STC-1 cell line treated with 0.2 μM sanguinarine; D: apoptosis assay results for the STC-1 cell line treated with 0.25 μM sanguinarine; E: apoptosis statistics for the STC-1 cell line treated with different concentrations of sanguinarine after three repetitions of the apoptosis experiment. Figure 4 Figures 2 and 3 show the effect of sanguinarine on apoptosis in H460 cells. A: apoptosis test results for the blank control group of H460 cells; B: apoptosis test results for H460 cells treated with 0.3 μM sanguinarine; C: apoptosis test results for H460 cells treated with 0.5 μM sanguinarine; D: apoptosis test results for H460 cells treated with 0.7 μM sanguinarine; E: statistical results of apoptosis after three repetitions of the apoptosis experiment in H460 cells treated with different concentrations of sanguinarine. Figure 5Figures show the results of the cell cycle arrest assay of neuroendocrine tumor cells STC-1. A: Cell cycle assay results of the blank control group of the STC-1 cell line; B: Cell cycle assay results of the STC-1 cell line treated with 0.15 μM sanguinarine; C: Cell cycle assay results of the STC-1 cell line treated with 0.2 μM sanguinarine; D: Cell cycle assay results of the STC-1 cell line treated with 0.25 μM sanguinarine; E: Cell cycle statistics of the STC-1 cell line treated with different concentrations of sanguinarine after three repetitions of the cell cycle experiment. Figure 6 Figures show the results of the cell cycle arrest test of neuroendocrine tumor cells H460 treated with sanguinarine. A: Cell cycle test results of the blank control group of the H460 cell line; B: Cell cycle test results of the H460 cell line treated with 0.3 μM sanguinarine; C: Cell cycle test results of the H460 cell line treated with 0.5 μM sanguinarine; D: Cell cycle test results of the H460 cell line treated with 0.7 μM sanguinarine; E: Cell cycle statistics of the H460 cell line treated with different concentrations of sanguinarine after three repetitions of the cell cycle experiment. Figure 7 Figures 2 and 3 show the test results of the effect of sanguinarine on the clone-forming ability of neuroendocrine tumor cells STC-1; A: STC-1 cell line blank control group cell clone-forming test results; B: STC-1 cell line 0.025 μM sanguinarine cell clone-forming test results; C: STC-1 cell line 0.05 μM sanguinarine cell clone-forming test results; D: STC-1 cell line 0.1 μM sanguinarine cell clone-forming test results; E: STC-1 cell line 0.2 μM sanguinarine cell clone-forming test results; F: STC-1 cell line 0.4 μM sanguinarine cell clone-forming test results. Figure 8 Figures 2 and 3 show the test results of the effect of sanguinarine on the clone-forming ability of neuroendocrine tumor cells H460; A: cell clone-forming test results of the blank control group of H460 cell line; B: cell clone-forming test results of the H460 cell line treated with 0.1 μM sanguinarine; C: cell clone-forming test results of the H460 cell line treated with 0.3 μM sanguinarine; D: cell clone-forming test results of the H460 cell line treated with 0.5 μM sanguinarine; E: cell clone-forming test results of the H460 cell line treated with 0.7 μM sanguinarine; F: cell clone-forming test results of the H460 cell line treated with 0.9 μM sanguinarine. DETAILED DESCRIPTION

[0025] In order to enable those skilled in the art to more clearly understand the technical solution of the present invention, the technical solution of the present invention will be described in detail below with reference to specific embodiments.

[0026] The following detailed descriptions are exemplary and are intended to provide further explanation of the present invention. Unless otherwise specified, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which the present invention belongs.

[0027] It should be noted that the terms used herein are intended only to describe specific embodiments and are not intended to limit the exemplary embodiments of the present invention. Experimental methods in the following examples, where specific conditions are not specified, were performed using conventional techniques in the art or in accordance with the conditions recommended by the manufacturer. Reagents and instruments used, where the manufacturer is not specified, are commercially available conventional products.

[0028] The cell lines used in the following examples are: Neuroendocrine tumor cell lines (e.g., STC-1, H460, etc.) were selected. These cell lines should have clear neuroendocrine tumor characteristics and be able to be stably cultured in vitro. 1) Cultivate the neuroendocrine tumor cell line under appropriate culture conditions to ensure that the cells are in a good growth state.

[0029] Experimental reagents and instruments: Prepare CCK-8 reagent, reagents required for flow cytometry (such as Annexin V / PI double staining reagent, PI staining reagent), reagents required for clone formation experiments (such as culture medium, crystal violet staining solution, etc.), as well as experimental instruments such as cell culture incubator, flow cytometer, microscope, etc.

[0030] Example 1: Study on the Effect of Sanguinarine on Neuroendocrine Tumor Cell Proliferation Taking neuroendocrine tumor cell lines STC-1 and H460 as examples, the CCK-8 assay was used to detect the effects of different concentrations of sanguinarine on the proliferation of neuroendocrine tumor cells.

[0031] The specific operation of the CCK-8 method is as follows: 1) Add 3×10 4Cells were suspended at 100 μl of a cell suspension (STC-1 or H460) at 5 cells / ml and incubated in a 96-well culture plate in an incubator (37°C, 5% CO2) for 24 hours. The 96-well culture plate was then divided into three groups: experimental wells, control wells, and blank wells. Experimental wells were treated by adding 100 μl of sanguinarine solution (the stock solution of sanguinarine is prepared by diluting it with culture medium to obtain different concentrations) diluted in culture medium to the experimental wells and incubating in an incubator (37°C, 5% CO2) for another 24 hours. Control wells were treated by adding 100 μl of culture medium to the control wells and incubating in an incubator (37°C, 5% CO2) for another 24 hours. Blank wells were treated without adding any substance, serving as blank controls.

[0032] 2) Add 10 μl of CCK-8 solution to the experimental and control wells of the 96-well culture plate treated in step 1) (be careful not to create bubbles in the wells, as these will affect the OD reading). Do not add CCK-8 solution to the blank wells. Then, incubate the 96-well culture plate in an incubator for 1-4 hours. After the incubation period, measure the absorbance of the experimental, control, and blank wells at 450 nm using a microplate reader.

[0033] Cell viability was calculated based on the absorbance test results using the formula: Cell viability = [(As-Ab) / (Ac-Ab)] × 100%; where As is the absorbance of the experimental well (containing cell suspension, CCK-8, and the test substance); Ac is the absorbance of the control well (containing cell suspension, CCK-8, and no test substance); and Ab is the absorbance of the blank well (culture medium without cell suspension, test substance, or CCK-8).

[0034] The experimental results are as follows Figure 1 、 Figure 2 As shown. Figure 1 、 Figure 2 Sanguinarine significantly inhibited the proliferation of STC-1 and H460 cell lines. Furthermore, as the concentration of sanguinarine increased, the inhibition rate of tumor cell proliferation also gradually increased, showing a clear dose-dependency. These results indicate that sanguinarine has a direct anti-proliferative effect on neuroendocrine tumor cells.

[0035] Example 2: Study on the Effect of Sanguinarine on Apoptosis of Neuroendocrine Tumor Cells Taking the neuroendocrine tumor cell lines STC-1 and H460 as examples, the effects of different concentrations of sanguinarine (0μmol / L, 0.15μmol / L, 0.2μmol / L, 0.25μmol / L, 0.3μmol / L, 0.5μmol / L, and 0.7μmol / L) on the apoptosis of neuroendocrine tumor cells were detected by flow cytometry.

[0036] The specific operation of detecting the effect of sanguinarine on neuroendocrine tumor cell apoptosis by flow cytometry is as follows: 1) Add 1.5×10 4 2 ml of cell suspension (STC-1 cell suspension or H460 cell suspension) with a concentration of 1 cell / ml was added, and the 6-well culture plates were cultured in an incubator (culture conditions were 37°C, 5% CO2) for 24 hours. The 6-well culture plates were then divided into a blank control group and a drug-added group. The blank control group was treated by continuing to culture in an incubator (culture conditions were 37°C, 5% CO2) for 24 hours.

[0037] The drug-addition group was treated as follows: after aspirating the culture medium in the 6-well culture plate, 2 ml of sanguinarine solution diluted with culture medium to different concentrations was added to the culture plate (the solvent of the sanguinarine stock solution is DMSO, and the sanguinarine stock solution was diluted with culture medium to obtain sanguinarine solutions of different concentrations). The cells were then cultured in an incubator (culture conditions: 37°C, 5% CO2) for 24 hours.

[0038] 2) Collect cells from the blank control and experimental groups: First, collect the culture medium from each well, then wash once with pre-chilled PBS. Add 0.5 ml of EDTA-free trypsin to each well for digestion. Add 0.5 ml of culture medium (containing 10% FBS) to terminate digestion, disperse the cells, and combine with the culture medium. Centrifuge at 1800 rpm for 5 minutes to pellet the cells, and discard the supernatant.

[0039] 3) Washing cells: Wash the cells twice with pre-chilled PBS, centrifuging each time at 1800 rpm (300 × g) at 4°C for 5 min.

[0040] 4) Resuspend cells: Add 100 μl of 1× Binding Buffer and gently pipette to create a single-cell suspension.

[0041] 5) Cell Staining: Add 5 μl of Annexin V-FITC / Annexin V-APC and 5 μl of PI Staining Solution and gently pipette to mix thoroughly. Incubate at room temperature (20-25°C) in the dark for 10 min. Add 400 μl of 1× Binding Buffer and gently mix. After staining, filter the sample through a 200-mesh sieve and analyze by flow cytometry within 1 hour.

[0042] The experimental results are as follows Figure 3 、 Figure 4 As shown. Figure 3 、 Figure 4 Sanguinarine treatment significantly increased the apoptosis rate of STC-1 and H460 cell lines. This suggests that sanguinarine may induce apoptosis in tumor cells by activating intracellular apoptotic signaling pathways, such as the mitochondrial pathway or the death receptor pathway. This finding provides an important cellular basis for the use of sanguinarine as an anti-tumor drug.

[0043] Example 3: Study on the Effect of Sanguinarine on Neuroendocrine Tumor Cell Cycle Arrest The neuroendocrine tumor cell lines STC-1 and H460 were used as examples to study the effects of different concentrations of sanguinarine solution on cell cycle arrest of neuroendocrine tumor cells.

[0044] The specific procedures for testing the effect of sanguinarine on neuroendocrine tumor cell cycle arrest are as follows: 1) Add 1.5×10 4 2 ml of cell suspension (STC-1 cell suspension or H460 cell suspension) with a concentration of 1 cell / ml was added, and the 6-well culture plates were cultured in an incubator (culture conditions were 37°C, 5% CO2) for 24 hours. The 6-well culture plates were then divided into a blank control group and a drug-added group. The blank control group was treated by continuing to culture in an incubator (culture conditions were 37°C, 5% CO2) for 24 hours.

[0045] The drug-addition group was treated as follows: after aspirating the culture medium in the 6-well culture plate, 2 ml of sanguinarine solution diluted with culture medium to different concentrations was added to the culture plate (the solvent of the sanguinarine stock solution is DMSO, and the sanguinarine stock solution was diluted with culture medium to obtain sanguinarine solutions of different concentrations) and cultured in an incubator (culture conditions: 37°C, 5% CO2) for 24 hours.

[0046] 2) Collect cells from the blank control group and the drug-treated group: First, collect the culture medium from each well, then wash once with pre-chilled PBS. Add 0.5 ml of trypsin to each well for digestion. Add 0.5 ml of culture medium (containing 10% FBS) to terminate digestion, disperse the cells, and combine with the culture medium. Centrifuge at 1800 rpm for 5 minutes to pellet the cells, and discard the supernatant. Resuspend the cells in 1 ml of pre-chilled PBS to adjust the cell concentration to 1 × 10 6 Take 1 ml of single cell suspension, centrifuge at 1000 rpm for 5 min, and discard the supernatant.

[0047] 3) After centrifugation of the prepared single-cell suspension and removal of the supernatant, add 500 µl of 70% pre-chilled ethanol to the cells and fix them in a 4°C refrigerator for 2 hours to overnight. Centrifuge at 1000 rpm for 5 minutes to remove the ethanol. Wash the cells with 1 ml of pre-chilled PBS and centrifuge at 1000 rpm for 5 minutes. Discard the supernatant.

[0048] 4) Add 100 µl of RNase A solution to the cell pellet, resuspend the cells, and incubate in a 37°C water bath for 30 min.

[0049] 5) Add 400 µl of PI staining solution, mix well, and incubate at 4°C in the dark for 30 min.

[0050] 6) After filtering through a 200-mesh sieve, the sample was tested on an instrument and the red fluorescence at an excitation wavelength of 488 nm was recorded.

[0051] The experimental results of sanguinarine on neuroendocrine tumor cell cycle arrest are as follows Figure 5 、 Figure 6 As shown. Figure 5 、 Figure 6 It can be seen that after sanguinarine treatment, neuroendocrine tumor cells are blocked in the G0 / G1 phase or G2 / M phase, which prevents the cells from entering the next cell cycle phase. This cell cycle arrest may help inhibit the proliferation and spread of tumor cells. Example 4: Study on the Effect of Sanguinarine on the Clone-forming Ability of Neuroendocrine Tumor Cells Taking the neuroendocrine tumor cell lines STC-1 and H460 as examples, the effect of sanguinarine on the clone-forming ability of neuroendocrine tumor cells was detected.

[0052] The specific operation for testing the cloning ability of sanguinarine on neuroendocrine tumor cells is as follows: 1) Add 1.5×10 32 ml of cell suspension (STC-1 cell suspension or H460 cell suspension) with a concentration of 1 cell / ml was added and cultured in an incubator (culture conditions were 37°C, 5% CO2) for 24 h. The 6-well culture plates were then divided into a blank control group and a drug-added group. The blank control group was treated by continuing to culture in an incubator (culture conditions were 37°C, 5% CO2) for 24 h.

[0053] The treatment method for the drug-dosing group was as follows: the culture medium in the culture wells was discarded, and then 2 ml of sanguinarine solution of different concentrations diluted with culture medium was added to the culture wells (the solvent of sanguinarine stock solution is DMSO, and the sanguinarine stock solution was diluted with culture medium to obtain sanguinarine solutions of different concentrations).

[0054] 2) Culture for 2 weeks until colonies are visible to the naked eye.

[0055] 3) After removing the culture medium, wash twice with PBS. Add 1 mL of 4% paraformaldehyde fixative to each well (for a 6-well plate) and fix for 15 minutes. However, longer fixation times, such as 1-2 hours, are also acceptable.

[0056] 4) Wash twice with distilled water for 2 minutes each time to remove residual paraformaldehyde.

[0057] 5) Stain with 0.1% crystal violet solution for 10-20 min (the time can be adjusted according to the staining results and requirements).

[0058] 6) After washing thoroughly with distilled water, you can observe and take pictures.

[0059] The results of the test on the clone formation ability of neuroendocrine tumor cells by sanguinarine are as follows Figure 7 、 Figure 8 As shown. Figure 7 、 Figure 8 As shown, compared with the control group, the number of colonies formed by STC-1 and H460 cell lines after sanguinarine treatment was significantly reduced, and the cloning rate was lowered. This indicates that sanguinarine can inhibit the self-renewal and proliferation ability of STC-1 and H460 cell lines, thereby reducing the risk of tumor recurrence and metastasis. Therefore, sanguinarine has an inhibitory effect on the cloning ability of neuroendocrine tumor cells.

[0060] Finally, it should be noted that the above embodiments are merely preferred embodiments of the present invention and are not intended to limit the present invention in any other manner. Any person skilled in the art may utilize the above technical content as a guide to make changes or modifications. These are equivalent embodiments of equivalent modifications. However, any simple modifications, equivalent changes, and modifications to the above embodiments that do not depart from the technical concept of the present invention and are based on the technical essence of the present invention remain within the scope of protection of the claims of the present invention.

Claims

1. Use of sanguinarine in the preparation of products for preventing, alleviating or / and treating neuroendocrine tumors.

2. Use of sanguinarine in the preparation of products for inhibiting the proliferation of neuroendocrine tumor cells.

3. Application of sanguinarine in the preparation of products for promoting apoptosis of neuroendocrine tumor cells.

4. Use of sanguinarine in the preparation of a product for blocking the cell cycle of neuroendocrine tumors.

5. Use of sanguinarine in the preparation of products for alleviating and / or treating inflammatory responses caused by neuroendocrine tumors.

6. The use according to any one of claims 1 to 5, characterized in that: The neuroendocrine tumors include gastroenteropancreatic neuroendocrine tumors and large cell lung cancer.

7. A product for alleviating and / or treating neuroendocrine tumors, characterized in that: The product contains sanguinarine and a neuroendocrine tumor therapeutic drug, wherein the neuroendocrine tumor therapeutic drug is a neuroendocrine tumor targeted therapeutic drug or a neuroendocrine tumor chemotherapy drug.

8. The product according to claim 7, characterized in that The neuroendocrine tumor targeted therapeutic drug is at least one of sunitinib, surufatinib, bevacizumab, and everolimus.

9. The product according to claim 7, characterized in that The chemotherapy drug for neuroendocrine tumors is at least one of temozolomide, cisplatin, etoposide, and streptozotocin.

10. The product according to any one of claims 7 to 9, characterized in that: The product also contains pharmaceutically acceptable excipients.

Images