Application of ginkgetin in enhancing VS4718 or ponatinib against esophageal squamous cell carcinoma progression

Abstract

The present invention provides the use of ginkgobilobaflavone in enhancing the anti-esophageal squamous cell carcinoma progression effect of VS4718 or ponatinib. The present invention discovers that ginkgobilobaflavone can enhance the inhibitory effects of VS4718 or ponatinib on the growth and invasion of esophageal squamous carcinoma cells; ginkgobilobaflavone sensitizes the inhibitory effects of VS4718 or ponatinib on the glycolipid metabolism of tumor cells, and the combination of ginkgobilobaflavone with VS4718 or ponatinib respectively produces a synergistic anti-cancer effect.

Description

Technical Field

[0001] The present invention relates to the field of pharmaceutical compositions. Specifically, the present invention relates to the use of ginkgetin in enhancing the anti-esophageal squamous cell carcinoma (ESCC) progression effect of VS4718 or ponatinib. Background Art

[0002] Esophageal squamous cell carcinoma (ESCC) is a solid tumor that seriously endangers human health worldwide and is also one of the highly prevalent and specific cancer types. With the improvement of the diagnosis and treatment level, the survival rate and survival status of ESCC patients have been improved, but the prognosis is still not ideal. Discovering new diagnostic markers and treatment strategies is crucial for targeting ESCC.

[0003] Tyrosine kinases can regulate various malignant phenotypes of ESCC by mediating the transmission of signaling pathways. Among them, the focal adhesion kinase (FAK) / Src signaling axis is an important signaling pathway promoting ESCC progression. Multiple small molecule inhibitors targeting the FAK / Src axis have been developed, but their anti-cancer effects still need to be further studied.

[0004] Small molecule monomer compounds of traditional Chinese medicine can inhibit the progression of tumor cells and reduce drug toxicity through multiple pathways and multiple targets, and thus synergistically. Therefore, the research on traditional Chinese medicine-assisted targeted drugs against ESCC has become the focus of current oncology research.

[0005] Ginkgetin is a biflavone from Ginkgo biloba and is a flavonoid compound with biological effects such as anti-inflammatory and antioxidant. Its structure is as follows:

[0006]

[0007] Ginkgetin has a wide range of biological activities, such as anti-inflammatory, antioxidant, and prevention of cardiovascular and cerebrovascular diseases. In recent years, it has also been reported that ginkgetin can inhibit various malignant phenotypes of solid tumor cell lines, such as growth, invasion and metastasis, and thus play an anti-cancer effect. However, there has been no research on ginkgetin enhancing the anti-cancer effects of FAK inhibitors and Src family kinase inhibitors. Summary of the Invention

[0008] The present invention discovers that ginkgetin has the effect of enhancing the anti-esophageal squamous cell carcinoma progression effect of FAK inhibitors and Src family kinase inhibitors. When ginkgetin is combined with FAK inhibitors or Src family kinase inhibitors, the drug combination can achieve a synergistic anti-cancer effect.

[0009] In a first aspect, the present invention provides a pharmaceutical composition comprising ginkgetin or a pharmaceutically acceptable salt thereof and a FAK inhibitor or a Src family kinase inhibitor.

[0010] In a second aspect, the present invention further provides a kit comprising ginkgetin or a pharmaceutically acceptable salt thereof and a FAK inhibitor or a Src family kinase inhibitor.

[0011] Preferably, the molar ratio of ginkgetin or a pharmaceutically acceptable salt thereof to a FAK inhibitor or a Src family kinase inhibitor is 1 - 30:1, preferably 3 - 8:1, more preferably 5:1.

[0012] Preferably, the FAK inhibitor includes VS4718 or a pharmaceutically acceptable salt thereof; the Src family kinase inhibitor includes ponatinib or a pharmaceutically acceptable salt thereof.

[0013] In the present invention, the CAS registration number of VS4718 is 1061353 - 68 - 1, and its chemical name is 2 - [[2-(2-methoxy-4-morpholin-4-ylanilino)-5-(trifluoromethyl)pyridin-4-yl]amino]-N-methylbenzamide (2 - [[2-(2-methoxy-4-morpholin-4-ylphenylamino)-5-(trifluoromethyl)pyridin-4-yl]amino]-N-methylbenzamide); the CAS registration number of ponatinib is 943319 - 70 - 8, and its chemical name is 3-(2-imidazo[1,2-b]pyridazin-3-ylethynyl)-4-methyl-N-[4-[(4-methyl-1-piperazinyl)methyl]-3-(trifluoromethyl)phenyl]benzamide (3-(2-imidazo[1,2-b]pyridazin-3-ylethynyl)-4-methyl-N-[4-[(4-methyl-1-piperazinyl)methyl]-3-(trifluoromethyl)phenyl]benzamide).

[0014] Preferably, the molar ratio of ginkgetin or a pharmaceutically acceptable salt thereof to VS4718 or a pharmaceutically acceptable salt thereof is 0.5 - 15:1, preferably 1 - 6:1, more preferably 2:1; the molar ratio of ginkgetin or a pharmaceutically acceptable salt thereof to ponatinib or a pharmaceutically acceptable salt thereof is 0.5 - 15:1, preferably 1 - 6:1, more preferably 2:1.

[0015] In a third aspect, the present invention further provides the use of the pharmaceutical composition in the preparation of a drug for preventing the progression of esophageal squamous cell carcinoma.

[0016] In a fourth aspect, the present invention provides the use of ginkgo biloba flavone or a pharmaceutically acceptable salt thereof in enhancing the anti-esophageal squamous cell carcinoma progression effect of a FAK inhibitor or a Src family kinase inhibitor.

[0017] In a fifth aspect, the present invention also provides the use of ginkgo biloba flavone or a pharmaceutically acceptable salt thereof in the preparation of a drug for enhancing the anti-esophageal squamous cell carcinoma progression effect of a FAK inhibitor or a Src family kinase inhibitor.

[0018] In the present invention, the anti-esophageal squamous cell carcinoma progression includes inhibiting the growth of esophageal squamous cell carcinoma cells, inhibiting the invasion of metastatic esophageal squamous cell carcinoma cells, inhibiting the glycolysis of esophageal squamous cell carcinoma cell lines, and inhibiting the fatty acid metabolism of esophageal squamous cell carcinoma cell lines.

[0019] In a preferred embodiment, the esophageal squamous cell carcinoma cells include esophageal squamous cell carcinoma KYSE410, esophageal squamous cell carcinoma cell line KYSE450, and esophageal squamous cell carcinoma KYSE510, and more preferably esophageal squamous cell carcinoma KYSE450.

[0020] In the present invention, the term "pharmaceutically acceptable salt" refers to a salt that retains the biological effectiveness and properties of the given compound and is not biologically or otherwise undesirable. Pharmaceutically acceptable salts include pharmaceutically acceptable base addition salts and pharmaceutically acceptable acid addition salts. Pharmaceutically acceptable base addition salts can be prepared from inorganic bases and organic bases. Salts derived from inorganic bases include (by way of example only) sodium, potassium, lithium, ammonium, calcium, and magnesium salts. Salts derived from organic bases include, but are not limited to, salts of primary amines, secondary amines, and tertiary amines, such as alkylamines, dialkylamines, trialkylamines, substituted alkylamines, bis(substituted alkyl)amines, tris(substituted alkyl)amines, alkenylamines, dialkenylamines, trialkenylamines, substituted alkenylamines, bis(substituted alkenyl)amines, tris(substituted alkenyl)amines, monocyclic alkylamines, bicyclic alkylamines or tricyclic alkylamines, monoarylamines, diarylamines or triarylamines or mixed amines, etc. Specific examples of suitable amines include (by way of example only) isopropylamine, trimethylamine, diethylamine, tris(isopropyl)amine, tris(n-propyl)amine, ethanolamine, 2-dimethylaminoethanol, piperazine, piperidine, morpholine, N-ethylpiperidine, etc. Pharmaceutically acceptable acid addition salts can be prepared from inorganic acids and organic acids. Inorganic acids from which salts can be derived include hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid, etc. Organic acids from which salts can be derived include acetic acid, propionic acid, glycolic acid, pyruvic acid, oxalic acid, malic acid, malonic acid, succinic acid, maleic acid, fumaric acid, tartaric acid, citric acid, benzoic acid, cinnamic acid, mandelic acid, methanesulfonic acid, ethanesulfonic acid, p-toluenesulfonic acid, salicylic acid, etc.

[0021] In one embodiment, the drug or pharmaceutical composition of the present invention further comprises a pharmaceutically acceptable carrier or excipient.

[0022] The term "pharmaceutically acceptable carrier or excipient" refers to a non-toxic inert solid, semi-solid or liquid filler, diluent, material for forming capsules, or any type of formulation aid. Some examples of materials that can serve as pharmaceutically acceptable carriers are sugars such as lactose, glucose, and sucrose; starches such as corn starch and potato starch; cellulose and its derivatives such as sodium carboxymethyl cellulose, ethyl cellulose, and cellulose acetate; powdered tragacanth; malt; gelatin; talc; excipients such as cocoa butter and suppository waxes; oils such as peanut oil, cottonseed oil, safflower oil, sesame oil, olive oil, corn oil, and soybean oil; glycols such as propylene glycol; esters such as ethyl oleate and ethyl laurate; agar; buffering agents such as magnesium hydroxide and aluminum hydroxide; alginic acid; pyrogen-free water; isotonic saline; Ringer's solution; ethanol; and phosphate buffers, and other non-toxic compatible lubricants such as sodium lauryl sulfate and magnesium stearate, as well as coloring agents, release agents, coating agents, sweetening agents, flavoring agents, and aromatic agents, etc.

[0023] The pharmaceutical compositions or drugs of the present invention can be administered orally, parenterally, by inhalation spray, topically, rectally, nasally, buccally, vaginally, or via an implant reservoir, preferably by oral administration or by injection. The term parenterally as used herein includes subcutaneous, intradermal, intravenous, intramuscular, intra-articular, intra-arterial, intrasynovial, intrasternal, intrathecal, intracutaneous, and intracranial injection or infusion techniques.

[0024] Solid dosage forms for oral administration include capsules, tablets, pills, powders, and granules. In such solid dosage forms, the active compound is admixed with at least one inert, pharmaceutically acceptable excipient or carrier (e.g., sodium citrate or calcium hydrogen phosphate) and / or: a) fillers or extenders such as starch, lactose, sucrose, glucose, mannitol, and silicic acid, b) binders such as carboxymethyl cellulose, alginates, gelatin, polyvinylpyrrolidone, sucrose, and acacia, c) wetting agents such as glycerol, d) disintegrating agents such as agar, calcium carbonate, potato or tapioca starch, alginic acid, certain silicates, and sodium carbonate, e) solution retarders such as paraffin, f) absorption promoters such as quaternary ammonium compounds, g) wetting agents such as cetyl alcohol and glycerol monostearate, h) adsorbents such as kaolin and bentonite, and i) lubricants such as talc, calcium stearate, magnesium stearate, solid polyethylene glycols, sodium lauryl sulfate, and mixtures thereof. In the case of capsules, tablets, and pills, buffering agents can also be included in the dosage form.

[0025] Liquid dosage forms for oral administration include pharmaceutically acceptable emulsions, microemulsions, solutions, suspensions, syrups, and elixirs. In addition to the active compound, the liquid dosage forms may contain inert diluents commonly used in the art, such as, for example, water or other solvents, solubilizing agents, and emulsifying agents, such as ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1,3-butanediol, dimethylformamide; oils (especially cottonseed, peanut, corn, germ, olive, castor, and sesame oils), glycerol, tetrahydrofurfuryl alcohol, polyethylene glycol, and fatty acid esters of sorbitan, and mixtures thereof. In addition to the inert diluents, the oral compositions may further include adjuvants, such as wetting agents, emulsifying agents, and suspending agents, sweetening agents, flavoring agents, and perfuming agents.

[0026] Injectable preparations (e.g., sterile injectable aqueous or oily suspensions) may be formulated according to known techniques using suitable dispersing or wetting agents and suspending agents. The sterile injectable preparation may also be a sterile injectable solution, suspension, or emulsion in a non-toxic parenterally acceptable diluent or solvent, such as a solution in 1,3-butanediol. Additionally, sterile, fixed oils are commonly used as a solvent or suspending medium. For this purpose, any bland fixed oil may be used, including synthetic mono- or diglycerides of fatty acids.

[0027] Dosage forms for topical or transdermal administration of the pharmaceutical compositions or drugs of the present invention include ointments, pastes, creams, lotions, gels, powders, solutions, sprays, inhalants, or patches. Under sterile conditions, the active ingredient is combined with a pharmaceutically acceptable carrier and any required preservatives or buffers as needed. Ophthalmic formulations, otic drops, eye ointments, powders, and solutions are also included within the scope of the present invention.

[0028] In one embodiment, the ginkgetin or a pharmaceutically acceptable salt thereof and the FAK inhibitor or Src family kinase inhibitor in the pharmaceutical composition, kit, or drug of the present invention may be administered in the same or different pharmaceutical formulations. The dosage forms of the ginkgetin or a pharmaceutically acceptable salt thereof and the FAK inhibitor or Src family kinase inhibitor may be the same or different. The ginkgetin or a pharmaceutically acceptable salt thereof and the FAK inhibitor or Src family kinase inhibitor may be administered simultaneously or sequentially.

[0029] In the medical uses described herein, for the administration time, administration frequency, and dosing frequency, etc. of the ginkgetin or a pharmaceutically acceptable salt thereof and the FAK inhibitor or Src family kinase inhibitor, it needs to be determined according to the specific diagnosis results of the condition, which is within the technical scope mastered by those skilled in the art.

[0030] For example, when applying a treatment regimen for mice or rats to humans, the effective dose of all drugs for humans can be converted from the effective dose of the drug for mice or rats, which is also easily achievable for those of ordinary skill in the art.

[0031] The drugs or pharmaceutical compositions of the present invention can be produced in a manner known to those skilled in the art, such as by dissolution, mixing, granulation, sugar coating preparation, grinding, emulsification, capsule formation, embedding, or freeze-drying processes.

[0032] Beneficial effects:

[0033] The present invention provides the application of ginkgetin in enhancing the anti-esophageal squamous cell carcinoma progression of VS4718 and ponatinib. Evaluated by the MTS method and soft agar colony formation assay, ginkgetin can enhance the growth inhibitory effect of VS4718 and ponatinib on esophageal squamous cell carcinoma KYSE450 cells. Evaluated by the Transwell method, ginkgetin can enhance the inhibitory effect of VS4718 and ponatinib on the invasion of esophageal squamous cell carcinoma cells. Ginkgetin significantly enhances the metabolism of VS4718 and ponatinib on esophageal squamous cell carcinoma cell line KYSE450, including reducing the contents of lactic acid, glucose, and fatty acids in ESCC cells. Ginkgetin combined with VS4718 and ponatinib respectively achieves a synergistic anti-esophageal squamous cell carcinoma effect, which is beneficial to improving the anti-tumor effect, thereby enhancing the anti-cancer activity of FAK inhibitors and Src family kinase inhibitors. Description of the drawings Description of the drawings:

[0035] Figure 1 Schematic diagram of the results that ginkgetin in Example 1 can enhance the inhibition of the growth of esophageal squamous cell carcinoma cell lines by VS4718 or ponatinib.

[0036] Figure 2 Schematic diagram of the results that ginkgetin in Example 2 can enhance the inhibition of the invasion of esophageal squamous cell carcinoma cell lines by VS4718 or ponatinib.

[0037] Figure 3 Schematic diagram of the results that ginkgetin in Example 3 enhances the inhibition of glucose metabolism of esophageal squamous cell carcinoma cell lines by VS4718 or ponatinib.

[0038] Figure 4 Schematic diagram of the results that ginkgetin in Example 4 enhances the inhibition of fatty acid metabolism of esophageal squamous cell carcinoma cell lines by VS4718 or ponatinib.

[0039] In the above figures, *** represents P < 0.001. Detailed implementation manners

[0040] The preferred examples of the invention will be described in detail below. The examples are provided to better present the content of the invention, but the content of the invention is not limited to the examples. Non-essential improvements and adjustments to the embodiments based on the content of the invention still fall within the scope of the invention.

[0041] In the following examples, the experimental methods are conventional methods unless otherwise specified. For those without specific technologies or conditions noted in the examples, they are carried out according to the technologies or conditions described in the literature in this field or according to the product specifications. Specific implementation mode:

[0043] Example 1: Ginkgobilobaflavone enhances the growth inhibitory effect of VS4718 or ponatinib on esophageal squamous cell carcinoma cell lines

[0044] 1. Cell culture

[0045] The human esophageal squamous cell carcinoma cell line KYSE450 was placed in RPMI1640 medium containing 10% fetal bovine serum and 1% penicillin-streptomycin. The incubator conditions were 37 °C and 5% CO2.

[0046] 2. Determination of cell growth ability (MTS method)

[0047] After inoculating the KYSE450 cell line (cultivation density of 3×10 3 cells / well) into a 96-well plate, ginkgobilobaflavone (1 μM), VS4718 (0.5 μM), ponatinib (0.5 μM) or their combination was added. After 72 hours, a 10% MTS solution was prepared with RPMI 1640 medium, added to the 96-well plate and incubated for 2 hours, and the absorbance value was measured at 490 nm with an enzyme-labeled instrument.

[0048] 3. Determination of cell growth ability (soft agar colony formation assay)

[0049] After preparing the lower agarose in a 96-well plate, the plate was left standing at 4 °C for 20 minutes. Then the upper agarose containing the KYSE450 cell line was prepared. After completing the preparation of the upper and lower agarose gels, a combination of ginkgobilobaflavone (1 μM) and VS4718 (0.5 μM) or ponatinib (0.5 μM) was added to the upper layer. After incubating for 8 days, a color development working solution was added, incubated at 37 °C for 4 hours, and the absorbance value was measured at 450 nm with an enzyme-labeled instrument.

[0050] Control attached Figure 1 , and the results showed that ginkgobilobaflavone could enhance the inhibition of the growth of esophageal squamous cell carcinoma cell lines by VS4718 or ponatinib.

[0051] Using Jin Zhengjun's Q - value judgment method, the synergistic effect of the combination of ginkgetin and VS4718 or ponatinib in inhibiting tumor growth was evaluated. The Q - value was calculated using the following formula: Q = E a+b / (E a +E b -E a ×E b ). E a+b is the inhibition rate of the drug combination, and E a and E b are the inhibition rates of drug treatment when administered alone. Q < 0.85 indicates antagonistic effect, 0.85 ≤ Q < 1.15 indicates additive effect, and Q ≥ 1.15 indicates synergistic effect.

[0052] After calculation, for the growth inhibitory effect mediated by the combination of ginkgetin and VS4718, the Q - value was 1.25; for the growth inhibitory effect mediated by the combination of ginkgetin and ponatinib, the Q - value was 1.22.

[0053] For the anchorage - independent growth inhibitory effect mediated by the combination of ginkgetin and VS4718, the Q - value was 1.31; for the anchorage - independent growth inhibitory effect mediated by the combination of ginkgetin and ponatinib, the Q - value was 1.25.

[0054] Example 2: Ginkgetin enhances the inhibitory effect of VS4718 or ponatinib on the invasion of esophageal squamous cell carcinoma cell lines

[0055] Detection of cell invasion ability:

[0056] The ability of ginkgetin to sensitize VS4718 and ponatinib against ESCC cell invasion was observed through the Tranwell system (8 - μm pore size). Add 100 μL of Matrigel to the upper chamber of the transwell chamber and incubate at 37 °C for 1 hour to solidify the Matrigel. Inoculate the prepared KYSE450 cell line into the upper chamber of the transwell chamber, add 800 μL of RPMI 1640 medium containing 20% fetal bovine serum to the lower chamber, and add ginkgetin (1 μM), VS4718 (0.5 μM), ponatinib (0.5 μM) or their combinations. Place the transwell chamber in an incubator and incubate for 24 hours. After taking it out, wipe the non - invasive KYSE450 cells in the upper chamber with a cotton swab. The KYSE450 cells that invaded into the lower chamber were separated by dissociation solution. The separated cells were added with dye, and after staining, the invasion cell rate was calculated by an enzyme - linked immunosorbent assay (ELISA) reader.

[0057] Control attached Figure 2 , and the results showed that ginkgetin could enhance the inhibition of VS4718 or ponatinib on the invasion of esophageal squamous cell carcinoma cell lines.

[0058] After calculation, for the inhibitory effect of ginkgetin combined with VS4718 on invasion, the Q value was 1.3; for the inhibitory effect of ginkgetin combined with ponatinib on invasion, the Q value was 1.27.

[0059] Example 3: Ginkgetin enhances the inhibitory effect of VS4718 or ponatinib on glucose metabolism in esophageal squamous cell carcinoma cell lines

[0060] The KYSE450 cell line was inoculated into 6-well plates. After the cells adhered, ginkgetin (1 μM), VS4718 (0.5 μM), ponatinib (0.5 μM), or their combinations were added. After 24 hours, the conditioned medium was collected. Using a lactate detection kit (Nanjing Jiancheng Bioengineering Institute Co., Ltd., product number: A019-3-1), after incubating the conditioned medium under different treatments with different reagents according to the reagent instruction manual, the absorbance was measured by a microplate reader and the lactate content was determined. Using a glucose detection kit (Beyotime Biotechnology Research Institute Co., Ltd., product number: S0201S), after incubating the conditioned medium under different treatments with different reagents according to the reagent instruction manual, the absorbance was measured by a microplate reader and the glucose content was determined.

[0061] Control attached Figure 3 , and the results showed that ginkgetin could enhance the inhibitory effect of VS4718 or ponatinib on glucose metabolism in esophageal squamous cell carcinoma cell lines.

[0062] After calculation, for the inhibitory effect of ginkgetin combined with VS4718 on lactate, the Q value was 1.32; for the inhibitory effect of ginkgetin combined with ponatinib on lactate, the Q value was 1.34. For the inhibitory effect of ginkgetin combined with VS4718 on glucose, the Q value was 1.31; for the inhibitory effect of ginkgetin combined with ponatinib on glucose, the Q value was 1.36.

[0063] Example 4: Ginkgetin enhances the inhibitory effect of VS4718 or ponatinib on fatty acid metabolism in esophageal squamous cell carcinoma cell lines

[0064] The KYSE450 cell line was inoculated into 6-well plates. After the cells adhered, ginkgetin (1 μM), VS4718 (0.5 μM), ponatinib (0.5 μM), or their combinations were added. After 24 hours, the conditioned medium was collected. Using a fatty acid detection kit (Nanjing Jiancheng Bioengineering Institute Co., Ltd., product number: A042-2-1), after incubating the conditioned medium under different treatments with different reagents according to the reagent instruction manual, the absorbance was measured by a microplate reader and the fatty acid content in the conditioned medium was determined.

[0065] Control attached Figure 4, The results showed that ginkgetin could enhance the inhibition of fatty acid metabolism in esophageal squamous cell lines by VS4718 or ponatinib.

[0066] Calculated, for the inhibitory effect of fatty acids mediated by the combination of ginkgetin and VS4718, the Q value was 1.26; for the inhibitory effect of fatty acids mediated by the combination of ginkgetin and ponatinib, the Q value was 1.22.

[0067] Finally, it should be noted that the above preferred embodiments are only used to illustrate the technical solutions of the present invention and not to limit them. 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. A pharmaceutical composition comprising ginkgetin or a pharmaceutically acceptable salt thereof and a FAK inhibitor, wherein, The FAK inhibitor is selected from VS4718 or a pharmaceutically acceptable salt thereof, and the molar ratio of ginkgetin or a pharmaceutically acceptable salt thereof to the FAK inhibitor is 1-6:

1. The pharmaceutical composition is used for resisting the progression of esophageal squamous cell carcinoma.

2. A kit, which comprises ginkgetin or a pharmaceutically acceptable salt thereof and a FAK inhibitor, wherein, The FAK inhibitor is selected from VS4718 or a pharmaceutically acceptable salt thereof, and the molar ratio of ginkgetin or a pharmaceutically acceptable salt thereof to the FAK inhibitor is 1-6:

1. The kit is used for resisting the progression of esophageal squamous cell carcinoma.

3. Use of the pharmaceutical composition according to claim 1 in the preparation of a drug for resisting the progression of esophageal squamous cell carcinoma.

4. The application according to claim 3, wherein The resisting the progression of esophageal squamous cell carcinoma includes inhibiting the growth of esophageal squamous cell carcinoma cells, inhibiting the invasion of metastatic esophageal squamous cell carcinoma cells, inhibiting the glucose metabolism of esophageal squamous cell carcinoma cell lines, and inhibiting the fatty acid metabolism of esophageal squamous cell carcinoma cell lines.

5. The application according to claim 4, characterized in that The esophageal squamous cell carcinoma cells include esophageal squamous cell carcinoma KYSE410, esophageal squamous cell carcinoma cell line KYSE450, and esophageal squamous cell carcinoma KYSE510.

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