EI24 agonist and its application in preparing a preparation for inhibiting the proliferation of esophageal squamous cell carcinoma

Abstract

The present invention belongs to the technical field of esophageal squamous cell carcinoma inhibitors, and particularly relates to an EI24 agonist and its application in the preparation of a preparation for inhibiting the proliferation of esophageal squamous cell carcinoma. The EI24 agonist is pentagalloyl glucose, FOXP1 protein or a combination of both. It can targetedly increase the expression level of EI24 and inhibit the proliferation of esophageal squamous cell carcinoma cells, and has good application prospects in inhibiting esophageal squamous cell carcinoma.

Description

Technical Field

[0001] The present invention belongs to the technical field of esophageal squamous cell carcinoma preparations, and particularly relates to an EI24 agonist and its application in the preparation of a preparation for inhibiting the proliferation of esophageal squamous cell carcinoma. Background Art

[0002] EI24 (etoposide-induced gene 24) is a DNA damage-related gene induced by etoposide and can be directly activated by the p53 gene. The EI24 protein is mainly located on the endoplasmic reticulum membrane and is an important protein that activates autophagy and participates in the formation of cell autophagy. At the same time, EI24 is also involved in biological processes such as apoptosis, proliferation, drug resistance, inflammation, cell metastasis, and epithelial-mesenchymal transformation.

[0003] Digestive tract tumors are characterized by difficult early diagnosis, easy recurrence and metastasis, and poor prognosis. Developing new and more specific digestive tract tumor marker molecules and therapeutic targets is of great significance for conquering digestive tract tumors. EI24 is a newly discovered tumor-related gene marker in recent years. It is involved in regulating many tumor biological processes, and the abnormal expression of E124 is closely related to the occurrence and development of digestive tract tumors such as pancreatic cancer, liver cancer, colorectal cancer, and esophageal cancer. Activating EI24 expression to inhibit tumor cell growth and make tumor cells sensitive to chemotherapy drugs is the key to developing tumor treatment drugs. However, the existing technology mainly focuses on the theoretical research on the high or low expression level of EI24 in tumor patients. For example, the content disclosed in documents such as "Wei Siyu, Hong Liu, Yang Wanli, etc. Research progress of EI24 in digestive tract tumors [J]. Journal of Modern Oncology, 2024(006):032". The R & D team members of the present invention have also been committed to the research on the EI24 expression level in tumor patients, but these have not been well translated into the actual application level, lacking an agonist that can effectively activate EI24. Summary of the Invention

[0004] To solve the above technical problems, the present invention provides an EI24 agonist and its application in the preparation of a preparation for inhibiting the proliferation of esophageal squamous cell carcinoma. Transforming theoretical research into the actual application level, promoting EI24 expression through the EI24 agonist, and showing the therapeutic sensitivity of esophageal squamous cell carcinoma.

[0005] The object of the present invention is to provide an EI24 agonist, which is pentagalloyl glucose, FOXP1 protein or a combination of the two.

[0006] When the EI24 agonist is a combination of pentagalloyl glucose and FOXP1 protein, the mass ratio of the two is 1:1 to 3.

[0007] Pentagalloyl glucose, FOXP1 protein, or a combination of the two both show the effect of activating EI24 expression, and are effective agonists for activating EI24, which can translate theoretical research into practical applications. By promoting EI24 expression with an EI24 agonist, it shows the therapeutic sensitivity to esophageal squamous cell carcinoma.

[0008] The present invention also provides a composition comprising an EI24 agonist, which is a combination of the EI24 agonist and an effect enhancer;

[0009] When the effect enhancer is combined with FOXP1 protein, the mass ratio of the two is 1:5 to 8.

[0010] When the effect enhancer is combined with pentagalloyl glucose, the mass ratio of the two is 1:6 to 10.

[0011] When the effect enhancer is combined with pentagalloyl glucose and FOXP1 protein, the mass ratio of the three is 1:3 to 5:3 to 5.

[0012] The effect enhancer is a substance that can increase the expression level of EI24; the effect enhancer is fructose. After being compounded with the EI24 agonist, fructose can enhance the effect of increasing the expression level of EI24. However, studies have shown that fructose alone cannot effectively increase the expression level of EI24, indicating that there is a process of mutual synergistic promotion in the compounding effect of fructose and the EI24 agonist.

[0013] Preferably, for the above composition, when the effect enhancer is combined with FOXP1 protein, the mass ratio of the two is 1:5.

[0014] Preferably, for the above composition, when the effect enhancer is combined with pentagalloyl glucose, the mass ratio of the two is 1:8.

[0015] Preferably, for the above composition, when the effect enhancer is combined with pentagalloyl glucose and FOXP1 protein, the mass ratio of the three is 1:4:4.

[0016] The present invention also provides an application of an EI24 agonist or a composition in the preparation of a preparation for inhibiting the proliferation of esophageal squamous cell carcinoma.

[0017] Preferably, for the above application, the inhibition of the proliferation of esophageal squamous cell carcinoma refers to inhibiting the proliferation of human esophageal cancer cells EC109 or human esophageal cancer cells EC9706.

[0018] Preferably, for the above application, the preparation is obtained by compounding the EI24 agonist with pharmaceutically acceptable excipients; or, the preparation is obtained by compounding the composition with pharmaceutically acceptable excipients.

[0019] Preferably, in the above application, the excipients include one or more of a filler, a disintegrant, a binder, a lubricant, a solubilizer, a stabilizer, and a surfactant.

[0020] For example, the filler is one or more of lactose, sucrose, and starch.

[0021] The disintegrant is one or more of sodium carboxymethyl cellulose or crospovidone.

[0022] The binder is gelatin or polyvinylpyrrolidone.

[0023] The lubricant is one or more of magnesium stearate, talc, and colloidal silicon dioxide.

[0024] The solubilizer is polyethylene glycol or propylene glycol.

[0025] The stabilizer is an antioxidant or a preservative to prevent the drug from denaturing or being contaminated. For example, the antioxidant is vitamin C or vitamin E, and the preservative is sodium benzoate or potassium sorbate.

[0026] The surfactant is Tween 80 or polysorbate 80.

[0027] The above are common pharmaceutically acceptable excipients. Without departing from the inventive concept of the present invention, substitutions made by those skilled in the art to the above excipients are regarded as equivalent substitutions.

[0028] Compared with the prior art, the present invention has the following beneficial effects:

[0029] An EI24 agonist provided by the present invention is pentagalloylglucose, FOXP1 protein, or a combination of the two. These substances or combinations of substances can targetedly increase the expression level of EI24 and inhibit the proliferation of esophageal squamous cell carcinoma. After further combination with fructose, the effect of activating the expression of EI24 is more obvious, and the effect of inhibiting the proliferation of esophageal squamous cell carcinoma is also more obvious, showing good application prospects in inhibiting the proliferation of esophageal squamous cell carcinoma. Brief Description of the Drawings

[0030] Figure 1 It is the analysis result of the clinical significance of EI24 expression in esophageal squamous cell carcinoma.

[0031] Among them, A, EI24 immunohistochemical staining scores of adjacent tissues and cancer tissues of esophageal squamous cell carcinoma; B, Kaplan-Meier survival curve drawn based on the EI24 expression level of esophageal squamous cell carcinoma patients, log-rank test: p = 0.0012.

[0032] Figure 2 It is the test result of ferroptosis of human esophageal cancer cell line EC109.

[0033] Figure 3 It is the experimental result of ferroptosis in human esophageal cancer cell line EC9706.

[0034] Figure 4 It is the experimental result of WB (Western Blot) treated with PGG.

[0035] Figure 5 It is the experimental result of WB after treating the esophageal squamous cell carcinoma mouse model EC109-EO.

[0036] Figure 6 It is the experimental result of WB after treating the esophageal squamous cell carcinoma mouse model EC109-NC. Detailed implementation manners

[0037] To enable those skilled in the art to better understand and implement the technical solutions of the present invention, the present invention will be further described below in conjunction with specific embodiments and drawings.

[0038] In the description of the present invention, unless otherwise specified, the reagents used are commercially available, and the methods used are conventional techniques in the art.

[0039] In the description of the present invention, pentagalloyl glucose was purchased from Chengdu Caoyuan Kang Biotechnology Co., Ltd. The FOXP1 protein is the FOXP1 recombinant protein purchased from Hubei Apt Biotechnology Co., Ltd., and the product name is FOXP1.

[0040] An EI24 agonist provided by the present invention is pentagalloyl glucose (PGG), FOXP1 protein (forkhead box protein P1), or a combination of the two.

[0041] These substances or combinations of substances can targetedly increase the expression level of EI24 and inhibit the proliferation of esophageal squamous cell carcinoma.

[0042] Based on the same inventive concept, the present invention provides a composition comprising an EI24 agonist, which is obtained by combining the EI24 agonist with an effect enhancer to obtain an agonist composition; the effect enhancer is fructose. When the effect enhancer is combined with the FOXP1 protein, the mass ratio of the two is 1:5-8; when the effect enhancer is combined with pentagalloyl glucose, the mass ratio of the two is 1:6-10; when the effect enhancer is combined with pentagalloyl glucose and the FOXP1 protein, the mass ratio of the two is 1:3-5:3-5.

[0043] Based on the same inventive concept, the present invention provides an application of an EI24 agonist in the preparation of a preparation for inhibiting the proliferation of esophageal squamous cell carcinoma.

[0044] The present invention provides an application of a composition containing an EI24 agonist in the preparation of a preparation for inhibiting the proliferation of esophageal squamous cell carcinoma.

[0045] The present invention includes the following embodiments.

[0046] Example 1

[0047] An EI24 agonist is pentagalloyl glucose.

[0048] Example 2

[0049] An EI24 agonist is FOXP1 protein.

[0050] Example 3

[0051] An EI24 agonist is obtained by mixing when pentagalloyl glucose and FOXP1 protein are combined, and the mass ratio of the two is 1:1.

[0052] Example 4

[0053] An EI24 agonist is obtained by mixing when pentagalloyl glucose and FOXP1 protein are combined, and the mass ratio of the two is 1:3.

[0054] Example 5

[0055] A composition is obtained by combining fructose and FOXP1 protein, and the mass ratio of fructose to FOXP1 protein is 1:5.

[0056] Example 6

[0057] A composition is obtained by combining fructose and FOXP1 protein, and the mass ratio of fructose to FOXP1 protein is 1:8.

[0058] Example 7

[0059] A composition is obtained by combining fructose and pentagalloyl glucose, and the mass ratio of fructose to pentagalloyl glucose is 1:8.

[0060] Example 8

[0061] A composition is obtained by combining fructose and pentagalloyl glucose, and the mass ratio of fructose to pentagalloyl glucose is 1:6.

[0062] Example 9

[0063] A composition is obtained by combining fructose and pentagalloyl glucose, and the mass ratio of fructose to pentagalloyl glucose is 1:10.

[0064] Example 10

[0065] A composition is composed of fructose, pentagalloylglucose, and FOXP1 protein, and the mass ratio of fructose, pentagalloylglucose, and FOXP1 protein is 1:4:4. The composition of this example is obtained by combining each material.

[0066] Example 11

[0067] A composition is composed of fructose, pentagalloylglucose, and FOXP1 protein, and the mass ratio of fructose, pentagalloylglucose, and FOXP1 protein is 1:3:3. The composition of this example is obtained by combining each material.

[0068] Example 12

[0069] A composition is composed of fructose, pentagalloylglucose, and FOXP1 protein, and the mass ratio of fructose, pentagalloylglucose, and FOXP1 protein is 1:5:5. The composition of this example is obtained by combining each material.

[0070] The effects of the present invention are illustrated below in conjunction with some experiments.

[0071] Experiment 1: EI24 is lowly expressed in esophageal squamous cell carcinoma, and low expression of EI24 is associated with poor prognosis of esophageal squamous cell carcinoma

[0072] According to the research results of "Duan L, Ma J, Yang W, et al. EI24 Inhibits Cell Proliferation and Drug Resistance of Esophageal Squamous Cell Carcinoma. [J]. Frontiers in oncology, 2020, 10:1570. DOI: 10.3389 / fonc.2020.01570", EI24 is lowly expressed in esophageal squamous cell carcinoma, and the survival rate of patients with esophageal squamous cell carcinoma is lower after low expression of EI24.

[0073] The present invention conducted research again with different samples, and the results are shown in Figure 1 , and integrating all the research results, it shows that EI24 is lowly expressed in esophageal squamous cell carcinoma, and low expression of EI24 is associated with poor prognosis of esophageal squamous cell carcinoma.

[0074] Experiment 2: EI24 promotes ferroptosis in esophageal squamous cell carcinoma

[0075] Test cells: human esophageal cancer cells EC109, human esophageal cancer cells EC9706.

[0076] Experimental method: When the above cells were cultured to 85% confluence, ferroptosis was induced by a ferroptosis inducer, and drug treatment was carried out simultaneously for 5 consecutive days. The OD450nm value of the cell lysate was counted every day. Among them, the drug treatment was set as follows:

[0077] EC109-LV-NC-EI24+DFO: Add 100 μL of 10 μg / L EI24 protein solution and 50 μL of 10 μg / L deferoxamine (DFO) to every 10 6 EC109 cells.

[0078] EC109-LV-NC: EC109 cells without drug treatment.

[0079] EC9706-LV-NC-EI24+DFO: Add 100 μL of 10 μg / L EI24 protein solution and 50 μL of 10 μg / L DFO to every 10 6 EC9706 cells.

[0080] EC9706-LV-NC: EC9706 cells without drug treatment.

[0081] Figure 2 Among them, EC109-LV-NC indicates that it has not been treated with EI24 protein and DFO, EC109-LV-NC-EI24 indicates that it has been treated with EI24 protein, and EC109-LV-NC-EI24+DFO indicates that it has been treated with EI24 protein and DFO. Figure 2 The results showed that after treatment with EI24 protein, the OD450 of EC109 cells decreased significantly. DFO is an iron chelator used to inhibit ferroptosis of EC109 cells and can also inhibit the death of EC109 cells caused by EI24 protein.

[0082] Figure 3 Among them, EC9706-LV-NC indicates that it has not been treated with EI24 protein and DFO, EC9706-LV-NC-EI24 indicates that it has been treated with EI24 protein, and EC9706-LV-NC-EI24+DFO indicates that it has been treated with EI24 protein and DFO. Figure 3 The results showed that after treatment with EI24 protein, the OD450 of EC9706 cells decreased significantly. DFO is used to inhibit ferroptosis of EC9706 cells and can also inhibit the death of EC9706 cells caused by EI24 protein.

[0083] Experiment 3: Experiment on increasing EI24 expression

[0084] The human esophageal cancer cell line EC109 was transplanted subcutaneously into immunodeficient mice to establish an esophageal squamous cell carcinoma mouse model EC109-EO. Additionally, the human esophageal cancer cell line EC9706 was transplanted subcutaneously into immunodeficient mice to establish an esophageal squamous cell carcinoma mouse model EC109-NC.

[0085] The esophageal squamous cell carcinoma mouse models EC109-EO or EC109-NC were treated with different concentrations of PGG, and the dosage of PGG was 100 μL / kg of mice. Using β-ACTIN as an internal reference, WB experiments were performed to measure the expression level of EI24. The results are shown in Figure 4 . The results showed that PGG treatment could increase the expression level of EI24, and with the increase of PGG concentration, the expression level of EI24 was higher.

[0086] The esophageal squamous cell carcinoma mouse models EC109-EO or EC109-NC were treated with FOXP1 protein, and the dosage of FOXP1 protein solution was 100 μL / kg of mice, with the concentration of FOXP1 protein solution being 10 μg / L. Using β-ACTIN as an internal reference, WB experiments were performed to measure the expression level of EI24. The results are shown in Figure 5 . The results showed that FOXP1 protein treatment could increase the expression level of EI24.

[0087] In addition, the esophageal squamous cell carcinoma mouse model EC109-EO was treated with the EI24 agonist of Example 3 and the compositions of Examples 5, 7, and 10; or the esophageal squamous cell carcinoma mouse model EC109-NC was treated with the EI24 agonist of Example 3 and the compositions of Examples 5, 7, and 10. The dosage of the EI24 agonist or the composition was 100 μL / kg of mice, and the concentration of the EI24 agonist or the composition was 10 μg / L. Using β-ACTIN as an internal reference, WB experiments were performed to measure the expression level of EI24. The results are shown in Figure 6 . The results showed that whether it was the combination of PGG and FOXP1 protein or adding fructose, the expression level of EI24 was significantly increased compared with the control group, and the bands were obvious.

[0088] Experiment 4: In vitro inhibition test of esophageal squamous cancer cells

[0089] Test cells: human esophageal cancer cells EC109, human esophageal cancer cells EC9706, and normal human esophageal cells HET-1A.

[0090] When the above cells were cultured to 85% confluence, the cells were treated with drugs, and the cell growth inhibition rate compared with that before drug treatment was calculated after 5 days of incubation. The drug addition settings were as follows:

[0091] Blank control: every 10 6Add 100 μL of 0.9% saline by mass to each 10 EC109 cells.

[0092] Positive control: Add 100 μL of DMSO with a concentration of 10 μg / L to each 10 6 EC109 cells.

[0093] Example 1 group: Add 100 μL of the EI24 agonist of Example 1 with a concentration of 10 μg / L to each 10 6 EC109 cells.

[0094] Example 2 group: Add 100 μL of the EI24 agonist of Example 2 with a concentration of 10 μg / L to each 10 6 EC109 cells.

[0095] Example 3 group: Add 100 μL of the EI24 agonist of Example 3 with a concentration of 10 μg / L to each 10 6 EC109 cells.

[0096] Example 4 group: Add 100 μL of the EI24 agonist of Example 4 with a concentration of 10 μg / L to each 10 6 EC109 cells.

[0097] Example 5 group: Add 100 μL of the composition of Example 5 with a concentration of 10 μg / L to each 10 6 EC109 cells.

[0098] Example 6 group: Add 100 μL of the composition of Example 6 with a concentration of 10 μg / L to each 10 6 EC109 cells.

[0099] Example 7 group: Add 100 μL of the composition of Example 7 with a concentration of 10 μg / L to each 10 6 EC109 cells.

[0100] Example 8 group: Add 100 μL of the composition of Example 8 with a concentration of 10 μg / L to each 10 6 EC109 cells.

[0101] Example 9 group: Add 100 μL of the composition of Example 9 with a concentration of 10 μg / L to each 10 6 EC109 cells.

[0102] Example 10 group: Add 100 μL of the composition of Example 10 with a concentration of 10 μg / L to each 10 6 EC109 cells.

[0103] Example 11 group: Add 100 μL of... to each 10 6Add 100 μL of the composition of Example 11 at a concentration of 10 μg / L to 10 EC109 cells.

[0104] Example 12 group: For every 10 6 Add 100 μL of the composition of Example 12 at a concentration of 10 μg / L to 10 EC109 cells.

[0105] Test method: The growth inhibition rate of cells was measured by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay.

[0106] Result processing: Each test was set up with 3 parallels, and the growth inhibition rate results were averaged.

[0107] Table 1 Results of cell growth inhibition rate I

[0108]

[0109] The results in Table 1 showed that the groups of Example 1 to Example 12 all had good inhibitory effects on human esophageal cancer cells EC109 and human esophageal cancer cells EC9706. And the inhibition rate on normal human esophageal cells HET-1A was low, indicating little damage to normal human esophageal cells HET-1A.

[0110] Test Five: Test of ferroptosis of esophageal cancer cells in vitro

[0111] Test cells: Human esophageal cancer cells EC109, human esophageal cancer cells EC9706.

[0112] When the above cells were cultured to 85% confluence, the cells were treated with drugs, and the cell growth inhibition rate compared with that before drug treatment was calculated after 5 days of incubation. The drug addition settings were as follows:

[0113] Blank control: Add 100 μL of normal saline with a mass fraction of 0.9% and 50 μL of 10 μg / L DFO to every 10 6 EC109 cells.

[0114] Positive control: Add 100 μL of DMSO at a concentration of 10 μg / L and 50 μL of 10 μg / L DFO to every 10 6 EC109 cells.

[0115] Example 1 group: Add 100 μL of the EI24 agonist of Example 1 at a concentration of 10 μg / L and 50 μL of 10 μg / L DFO to every 10 6 EC109 cells.

[0116] Example 2 group: For every 10 6Add 100 μL of the EI24 agonist of Example 2 at a concentration of 10 μg / L and 50 μL of DFO at a concentration of 10 μg / L to every 10 EC109 cells.

[0117] Example 3 group: Every 10 6 Add 100 μL of the EI24 agonist of Example 3 at a concentration of 10 μg / L and 50 μL of DFO at a concentration of 10 μg / L to every 10 EC109 cells.

[0118] Example 4 group: Every 10 6 Add 100 μL of the EI24 agonist of Example 4 at a concentration of 10 μg / L and 50 μL of DFO at a concentration of 10 μg / L to every 10 EC109 cells.

[0119] Example 5 group: Every 10 6 Add 100 μL of the composition of Example 5 at a concentration of 10 μg / L and 50 μL of DFO at a concentration of 10 μg / L to every 10 EC109 cells.

[0120] Example 6 group: Every 10 6 Add 100 μL of the composition of Example 6 at a concentration of 10 μg / L and 50 μL of DFO at a concentration of 10 μg / L to every 10 EC109 cells.

[0121] Example 7 group: Every 10 6 Add 100 μL of the composition of Example 7 at a concentration of 10 μg / L and 50 μL of DFO at a concentration of 10 μg / L to every 10 EC109 cells.

[0122] Example 8 group: Every 10 6 Add 100 μL of the composition of Example 8 at a concentration of 10 μg / L and 50 μL of DFO at a concentration of 10 μg / L to every 10 EC109 cells.

[0123] Example 9 group: Every 10 6 Add 100 μL of the composition of Example 9 at a concentration of 10 μg / L and 50 μL of DFO at a concentration of 10 μg / L to every 10 EC109 cells.

[0124] Example 10 group: Every 10 6 Add 100 μL of the composition of Example 10 at a concentration of 10 μg / L and 50 μL of DFO at a concentration of 10 μg / L to every 10 EC109 cells.

[0125] Example 11 group: Every 10 6 Add 100 μL of the composition of Example 11 at a concentration of 10 μg / L and 50 μL of DFO at a concentration of 10 μg / L to every 10 EC109 cells.

[0126] Example 12 group: Every 106 Add 100 μL of the composition of Example 12 at a concentration of 10 μg / L and 50 μL of 10 μg / L DFO to each EC109 cell.

[0127] Test method: The growth inhibition rate of cells was determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay.

[0128] Result processing: Each test was set up with 3 parallels, and the growth inhibition rate results were averaged. The results in Table 2 showed that in the in vitro ferroptosis tests of esophageal cancer cells in the groups of Example 1 to Example 12, good inhibitory effects on human esophageal cancer cells EC109 and human esophageal cancer cells EC9706 were achieved, and the cell mortality rate was high.

[0129] Table 2 Results of cell growth inhibition rate II

[0130]

[0131]

[0132] It should be noted that when the present invention involves numerical ranges, it should be understood that any value between the two endpoints of each numerical range and the two endpoints can be selected. Since the steps and methods adopted are the same as those in the examples, in order to prevent repetition, the present invention describes the preferred examples. Although the preferred embodiments of the present invention have been described, once those skilled in the art know the basic inventive concept, additional changes and modifications can be made to these embodiments, and these changes and modifications all fall within the scope of the present invention.

[0133] Obviously, those skilled in the art can make various changes and modifications to the present invention without departing from the spirit and scope of the present invention. If these modifications and variations of the present invention fall within the scope of the equivalent technology of the present invention, the present invention also intends to include these changes and deformations.

Claims

1. A composition comprising an EI24 agonist, characterized in that The EI24 agonist is pentagalloyl glucose, FOXP1 protein or a combination of the two; When the EI24 agonist is composed of pentagalloylglucose and FOXP1 protein, the mass ratio of the two is 1:1~3; The composition is a combination of an EI24 agonist and an effect enhancer; When the effect enhancer and the FOXP1 protein are combined, the mass ratio of the two is 1:5-8; When the effect enhancer is combined with the pentagalloylglucose, the mass ratio of the two is 1:6-10; When the effect enhancer, the pentagalloylglucose and the FOXP1 protein are combined, the mass ratio of the three is 1:3-5:3-5; The effect enhancer is fructose.

2. The composition according to claim 1, characterized in that When the effect enhancer and the FOXP1 protein are combined, the mass ratio of the two is 1:

5.

3. The composition according to claim 1, characterized in that When the effect enhancer is combined with the pentagalloylglucose, the mass ratio of the two is 1:

8.

4. The composition according to claim 1, characterized in that When the effect enhancer, the pentagalloylglucose and the FOXP1 protein are combined, the mass ratio of the three is 1:4:

4.

5. Use of the composition according to claim 1 in preparing a preparation for inhibiting the proliferation of esophageal squamous cell carcinoma.

6. The use according to claim 5, characterized in that: The inhibition of esophageal squamous cell carcinoma proliferation refers to the inhibition of proliferation of human esophageal cancer cells EC109 or human esophageal cancer cells EC9706.

7. The use according to claim 5, characterized in that: The preparation is obtained by compounding the composition with pharmaceutically acceptable excipients.

8. The use according to claim 7, characterized in that: The auxiliary materials include one or more of fillers, disintegrants, binders, lubricants, cosolvents, stabilizers and surfactants.

9. The use according to claim 8, characterized in that: The filler is one or more of lactose, sucrose and starch; The disintegrant is one or more of sodium carboxymethylcellulose or cross-linked polyvinylpyrrolidone; The adhesive is gelatin or polyvinyl pyrrolidone; The lubricant is one or more of magnesium stearate, talcum powder, and micro-powdered silica gel; The cosolvent is polyethylene glycol or propylene glycol; The stabilizer is an antioxidant or a preservative; The surfactant is Tween 80.

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