Application of Chrysin Sensitizing VS4718 or Ponatinib in the Treatment of Esophageal Squamous Cell Carcinoma

Abstract

The present invention provides the use of chrysin to enhance the sensitization of VS4718 or ponatinib in the treatment of esophageal squamous cell carcinoma. The present invention finds that chrysin can enhance the growth inhibition and invasion inhibition of esophageal squamous cell carcinoma cells mediated by VS4718 or ponatinib, and can effectively enhance the tumor metabolism inhibition mediated by VS4718 or ponatinib. Chrysin is used in combination with VS4718 or ponatinib to produce a synergistic anti-cancer effect.

Description

Technical Field

[0001] The present invention relates to the field of pharmaceutical compositions, and in particular to the use of chrysin to enhance the sensitivity of VS4718 or ponatinib in the treatment of esophageal squamous cell carcinoma. Background Art

[0002] Esophageal cancer is a solid tumor that seriously endangers human health worldwide. From the perspective of histological type, esophageal cancer is mainly divided into two types: esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma. The occurrence and development of ESCC is regulated by multiple factors. At present, although interdisciplinary research such as epidemiology, etiology, diagnosis and molecular biology has made certain progress. However, the prevention and treatment of ESCC is still very severe. Clinical ESCC treatment mainly uses conventional chemotherapy drugs and some immunotherapy, but tumor recurrence and metastasis are very likely to occur after treatment. How to discover new targets and study their targeted drugs against ESCC is very important in improving drug anti-ESCC.

[0003] Focal adhesion kinase (FAK) and its interacting molecule Src are a class of cytoplasmic non-receptor protein tyrosine kinases (PTKs) belonging to the protein tyrosine kinase superfamily. The FAK / Src signaling axis plays a pivotal role in cell signal transduction, promoting tumorigenesis and invasion and metastasis by coordinating intracellular and extracellular signals. Several small molecule kinase inhibitors targeting FAK and Src, especially the FAK inhibitor VS4718 and the Src inhibitor ponatinib, have been used in clinical trials, but their anti-ESCC effects still need further study.

[0004] In recent years, Chinese medicine has been widely used by researchers to combine with other drugs to enhance synergy and reduce toxicity due to its comprehensive effects of multiple components, multiple pathways and multiple targets. Some Chinese medicines also have anti-tumor effects, so the research on the anti-tumor effect of Chinese medicine-assisted chemotherapy drugs has become a current hot topic.

[0005] Chrysin (CHR) is a type of flavonoid small molecule compound, mainly distributed in Oroxylum indica and propolis of Bignoniaceae. Its structural formula is as follows:

[0006]

[0007] Chrysin has a wide range of biological activities, such as anti-inflammatory, anti-oxidant, and prevention of cardiovascular and cerebrovascular diseases. In recent years, it has also been reported that chrysin has an anti-cancer effect by inhibiting the growth of tumor cells. However, there has been no research on chrysin enhancing the anti-cancer effect of FAK inhibitors and Src family kinase inhibitors. Summary of the invention

[0008] The present invention finds that when chrysin is used in combination with a FAK inhibitor or a Src family kinase inhibitor, chrysin can greatly enhance the anti-esophageal squamous cell carcinoma effects of the FAK inhibitor and the Src family kinase inhibitor, achieving a synergistic effect.

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

[0010] The present invention also provides a kit, which comprises chrysin or a pharmaceutically acceptable salt thereof and a FAK inhibitor or a Src family kinase inhibitor.

[0011] Preferably, the molar ratio of chrysin or a pharmaceutically acceptable salt thereof to the FAK inhibitor or the Src family kinase inhibitor is 5-50:1, preferably 20-30:1, and more preferably 25:1.

[0012] Preferably, the FAK inhibitor includes VS4718 or a pharmaceutically acceptable salt thereof; and 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 the chemical name is 2-[[2-(2-methoxy-4-morpholin-4-ylanilino)-5-(trifluoromethyl)pyridin-4-yl]

[0014] amino]-N-methylbenzamide (2-[[2-(2-methoxy-4-morpholinyl-4-ylanilino)-5-(trifluoromethyl)pyridinyl-4-yl]amino]-N-methylbenzamide); the CAS registration number of Ponatinib is 943319-70-8, and the chemical name is 3-(2-imidazo[1,2-b]pyridazin-3-ylethynyl)-4-methyl

[0015] -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).

[0016] Preferably, the molar ratio of chrysin or a pharmaceutically acceptable salt thereof to VS4718 or a pharmaceutically acceptable salt thereof is 5-50:1, preferably 20-30:1, and more preferably 25:1; the molar ratio of chrysin or a pharmaceutically acceptable salt thereof to ponatinib or a pharmaceutically acceptable salt thereof is 5-50:1, preferably 20-30:1, and more preferably 25:1.

[0017] In addition, the present invention also provides the use of the pharmaceutical composition in preparing a drug for treating esophageal squamous cell carcinoma.

[0018] In another aspect, the present invention provides a use of chrysin or a pharmaceutically acceptable salt thereof in enhancing the effect of a FAK inhibitor or a Src family kinase inhibitor in treating esophageal squamous cell carcinoma.

[0019] Finally, the present invention also provides the use of chrysin or a pharmaceutically acceptable salt thereof in the preparation of a drug, wherein the drug is used to enhance the effect of a FAK inhibitor or a Src family kinase inhibitor in the treatment of esophageal squamous cell carcinoma.

[0020] In the present invention, the treatment 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 sugar metabolism of esophageal squamous cell carcinoma cell lines, and inhibiting the fatty acid metabolism of esophageal squamous cell carcinoma cell lines.

[0021] In a preferred embodiment, the esophageal squamous cell carcinoma cells include esophageal squamous cell carcinoma cell line KYSE410, esophageal squamous cell carcinoma cell line KYSE450, and esophageal squamous cell carcinoma cell line KYSE510, and more preferably esophageal squamous cell carcinoma cell line KYSE450.

[0022] In the present invention, the term "pharmaceutically acceptable salt" refers to a salt that retains the biological effectiveness and properties of a 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, di(substituted alkyl)amines, tri(substituted alkyl)amines, alkenylamines, dienylamines, trialnylamines, substituted alkenylamines, di(substituted alkenyl)amines, tri(substituted alkenyl)amines, monocyclic alkylamines, dicyclic alkylamines or tricyclic alkylamines, monoarylamines, diarylamines or triarylamines or salts of mixed amines, etc. Specific examples of suitable amines include, by way of example only, isopropylamine, trimethylamine, diethylamine, tri(isopropyl)amine, tri(n-propyl)amine, ethanolamine, 2-dimethylaminoethanol, piperazine, piperidine, morpholine, N-ethylpiperidine, and the like. Pharmaceutically acceptable acid addition salts can be prepared from inorganic and organic acids. Inorganic acids from which salts can be derived include hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid, and the like. 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, and the like.

[0023] In one embodiment, the medicament or pharmaceutical composition of the present invention further comprises a pharmaceutically acceptable carrier or excipient.

[0024] The term "pharmaceutically acceptable carrier or excipient" refers to a non-toxic, inert solid, semisolid or liquid filler, diluent, encapsulating material or formulation auxiliary of any type. 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 carboxymethylcellulose, ethylcellulose 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; buffers such as magnesium hydroxide and aluminum hydroxide; alginic acid; pyrogen-free water; isotonic saline; Ringer's solution; ethanol and phosphate buffers, and other nontoxic compatible lubricants such as sodium lauryl sulfate and magnesium stearate, as well as colorants, release agents, coating agents, sweeteners, flavoring agents and perfuming agents and the like.

[0025] The pharmaceutical composition or medicament of the present invention can be administered orally, parenterally, by inhalation spray, topically, rectally, nasally, to the cheek, vaginally or through an implanted reservoir, preferably by oral administration or by injection. The term parenteral as used herein includes subcutaneous, intracutaneous, intravenous, intramuscular, intraarticular, intraarterial, intrasynovial, intrasternal, intrathecal, intrawound and intracranial injection or infusion techniques.

[0026] Solid dosage forms for oral administration include capsules, tablets, pills, powders and granules. In such solid dosage forms, the active compound is mixed with at least one inert, pharmaceutically acceptable excipient or carrier (e.g., sodium citrate or dibasic calcium phosphate) and / or: a) fillers or expanders such as starch, lactose, sucrose, glucose, mannitol and silicic acid, b) binders such as carboxymethylcellulose, alginates, gelatin, polyvinylpyrrolidone, sucrose and acacia, c) wetting agents such as glycerol, d) disintegrants such as agar, calcium carbonate, potato or tapioca starch, alginic acid, certain silicates and sodium carbonate, e) solution retarder such as paraffin, f) absorption promoters such as quaternary ammonium compounds, g) wetting agents such as cetyl alcohol and glyceryl monostearate, h) absorbents such as clay and bentonite, and i) lubricants such as talc, calcium stearate, magnesium stearate, solid polyethylene glycol, sodium lauryl sulfate and mixtures thereof. In the case of capsules, tablets and pills, the dosage form may also comprise buffering agents.

[0027] 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 form may contain inert diluents commonly used in the art, for example, water or other solvents, solubilizers and emulsifiers, such as ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1,3-butylene glycol, 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 inert diluents, oral compositions may also include adjuvants, such as wetting agents, emulsifiers and suspending agents, sweeteners, flavoring agents and aromatics.

[0028] Injectable preparations (e.g., sterile injectable aqueous or oily suspensions) can be prepared according to known techniques using appropriate dispersants or wetting agents and suspending agents. Sterile injectable preparations can also be sterile injectable solutions, suspensions or emulsions in nontoxic parenterally acceptable diluents or solvents, such as solutions in 1,3-butanediol. In addition, sterile fixed oils are usually used as solvents or suspending media. For this purpose, any bland fixed oil can be used, including synthetic mono- or di-glycerides.

[0029] The dosage form of the pharmaceutical composition of the present invention or the medicine administered topically or percutaneously comprises ointment, paste, cream, lotion, gel, powder, solution, spray, inhalant or patch. Under aseptic conditions, the active ingredient is mixed with a pharmaceutically acceptable carrier and any required preservative or required buffer. Ophthalmic preparations, ear drops, eye ointments, powders and solutions are also included within the scope of the present invention.

[0030] In one embodiment, the chrysin or its pharmaceutically acceptable salt and the FAK inhibitor or Src family kinase inhibitor in the pharmaceutical composition, kit or medicine of the present invention can be administered in the same or different pharmaceutical preparations. The pharmaceutical dosage forms of chrysin or its pharmaceutically acceptable salt and the FAK inhibitor or Src family kinase inhibitor can be the same or different. Chrysin or its pharmaceutically acceptable salt and the FAK inhibitor or Src family kinase inhibitor can be administered simultaneously or sequentially.

[0031] In the medical uses described herein, the administration time, number of administrations and frequency of administration of chrysin or its pharmaceutically acceptable salt and FAK inhibitor or Src family kinase inhibitor, etc., need to be determined according to the specific diagnosis results of the disease, which is within the technical scope mastered by those skilled in the art.

[0032] For example, when a treatment regimen for mice or rats is applied to humans, the effective doses of all drugs for humans can be converted by the effective doses of the drugs for mice or rats, which is also easy to achieve for ordinary technicians in this field.

[0033] The medicament or pharmaceutical composition of the present invention can be produced in a manner known to those skilled in the art, for example, by dissolving, mixing, granulating, dragee-making, levigating, emulsifying, encapsulating, entrapping or lyophilizing processes. Beneficial Effects

[0034] The present invention provides the use of chrysin to enhance the sensitization of VS4718 and ponatinib in the treatment of esophageal squamous cell carcinoma. As evaluated by the MTS method and soft agar clone formation experiment, chrysin can enhance the growth inhibition of esophageal squamous cell carcinoma cell KYSE450 mediated by VS4718 and ponatinib. As evaluated by the Transwell method, chrysin can enhance the invasion inhibition of esophageal squamous cell carcinoma cell mediated by VS4718 and ponatinib. Chrysin significantly enhances the metabolism of VS4718 and ponatinib on esophageal squamous cell carcinoma cell line KYSE450, including reducing the content of lactate, glucose and fatty acids in ESCC cells. Chrysin is used in combination with VS4718 and ponatinib, respectively, to achieve a synergistic anti-esophageal squamous cell carcinoma effect, thereby reducing the dosage of drugs and reducing the patient's resistance to FAK inhibitors and Src family kinase inhibitors. BRIEF DESCRIPTION OF THE DRAWINGS

[0035] Figure 1 This is a schematic diagram showing the results that chrysin in Example 1 can enhance the growth inhibition of esophageal squamous cell carcinoma cell lines by VS4718 or ponatinib.

[0036] Figure 2 This is a schematic diagram showing the results that chrysin in Example 2 can enhance the ability of VS4718 or ponatinib to inhibit the invasion of esophageal squamous cell carcinoma cell lines.

[0037] Figure 3 This is a schematic diagram of the results of Example 3 showing that chrysin enhances the inhibition of glucose metabolism by VS4718 or ponatinib in esophageal squamous cell carcinoma cell lines.

[0038] Figure 4 This is a schematic diagram of the results of Example 4 showing that chrysin enhances the inhibition of fatty acid metabolism of ESCC cell lines by VS4718 or Ponatinib.

[0039] In the above figures, Represents P < 0.001. DETAILED DESCRIPTION

[0040] 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.

[0041] 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.

[0042] Example 1: Chrysin enhances the growth inhibitory effect of VS4718 or Ponatinib on esophageal squamous cell carcinoma cell lines

[0043] 1. Cell Culture

[0044] Human esophageal squamous cell carcinoma cell line KYSE450 was cultured in RPMI 1640 medium containing 10% fetal bovine serum and 1% penicillin-streptomycin. The incubator temperature was 37°C and contained 5% CO2.

[0045] 2. Cell growth ability determination (MTS method)

[0046] KYSE450 cell line (3×10 3 The cells were evenly seeded in a 96-well plate at a density of 100 cells / well. After the cells adhered to the wall, chrysin (12.5 μM) and / or VS4718 (0.5 μM) and ponatinib (0.5 μM) were added. Three days later, MTS solution was added to the 96-well plate and incubated for 2 hours. The absorbance value was measured at 490 nm using a microplate reader.

[0047] 3. Cell growth ability determination (soft agar colony formation assay)

[0048] After the lower agarose layer is prepared in a 96-well plate (it is placed at 4°C for 15 minutes after preparation), the upper agarose layer (containing KYSE450 cells) is prepared. After the upper and lower agarose layers are prepared, chrysin (12.5 μM) and VS4718 (0.5 μM) or ponatinib (0.5 μM) are added, incubated for 8 days, and then the color developing solution is added. After incubation at room temperature, the absorbance value at 450 nm is measured using an ELISA reader.

[0049] Compare with Figure 1 , the results showed that chrysin could enhance the growth inhibition of ESCC cell lines by VS4718 or ponatinib.

[0050] The Jin Zhengjun Q value judgment method was used to evaluate the synergistic effect of the combination of chrysin and VS4718 or ponatinib in inhibiting tumor growth. The Q value was calculated using the following formula: Q = E a+b / (E a +E b -E a ×E b ). a+b is the inhibition rate of the drug combination, E a and E b It is the inhibition rate of drug treatment when administered alone. Q<0.85 indicates antagonism, 0.85≤Q<1.15 indicates additive effect, and Q≥1.15 indicates synergistic effect.

[0051] After calculation, in the MTS method, the Q value for the growth inhibitory effect mediated by chrysin combined with VS4718 was 1.18; the Q value for the growth inhibitory effect mediated by chrysin combined with ponatinib was 1.25.

[0052] In the soft agar colony formation experiment, the Q value for the non-anchorage-dependent growth inhibition effect mediated by chrysin combined with VS4718 was 1.2; the Q value for the non-anchorage-dependent growth inhibition effect mediated by chrysin combined with ponatinib was 1.17.

[0053] Example 2: Chrysin enhances the inhibitory effect of VS4718 or Ponatinib on the invasion of esophageal squamous cell carcinoma cell lines

[0054] Cell invasion ability detection:

[0055] KYSE450 cells were incubated in serum-free RPMI 1640 medium for 24 hours. Using a transwell system 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. After the Matrigel solidified, the KYSE450 cell line was inoculated in the upper chamber of the transwell, and 800 μL of RPMI 1640 medium containing 20% ​​serum was added to the lower chamber. Chrysin (12.5 μM) and / or VS4718 (0.5 μM) and Ponatinib (0.5 μM) were added to the transwell system and incubated in an incubator for 24 hours. After removal, the KYSE450 cells that did not penetrate the inner wall of the upper chamber were wiped clean with a cotton swab. The invasive cells in the lower chamber were separated by dissociation solution and then cell dye was added. The invasion cell rate was calculated by an ELISA instrument.

[0056] Compare with Figure 2 , the results showed that chrysin could enhance the inhibition of VS4718 or ponatinib on the invasion of esophageal squamous cell carcinoma cell lines.

[0057] After calculation, the Q value for the invasion inhibition effect mediated by chrysin combined with VS4718 was 1.15; the Q value for the invasion inhibition effect mediated by chrysin combined with ponatinib was 1.17.

[0058] Example 3: Chrysin enhances the inhibitory effect of VS4718 or Ponatinib on glucose metabolism in esophageal squamous cell carcinoma cell lines

[0059] KYSE450 cell lines were inoculated in 6-well plates. After the cells adhered to the wall, chrysin (12.5 μM) and / or VS4718 (0.5 μM) and ponatinib (0.5 μM) were added. After 1 day, the conditioned medium was collected and incubated with different reagents according to the instructions of the reagent manual using a lactate detection kit (Nanjing Jiancheng Bioengineering Research Institute Co., Ltd., Catalog No.: A019-3-1). The absorbance was measured in an ELISA instrument to observe the lactate content. The glucose detection kit (Biyuntian Biotechnology Research Institute Co., Ltd., Catalog No.: S0201S) was used to incubate the collected conditioned medium with different reagents in sequence according to the instructions of the reagent manual. The absorbance was displayed on an ELISA instrument and the glucose content was measured.

[0060] Compare with Figure 3 , the results showed that chrysin could enhance the inhibition of glucose metabolism by VS4718 or ponatinib in esophageal squamous cell carcinoma cell lines.

[0061] After calculation, the Q value for the lactate inhibition effect mediated by chrysin combined with VS4718 was 1.25, and the Q value for the lactate inhibition effect mediated by chrysin combined with ponatinib was 1.18. The Q value for the glucose inhibition effect mediated by chrysin combined with VS4718 was 1.24, and the Q value for the glucose inhibition effect mediated by chrysin combined with ponatinib was 1.19.

[0062] Example 4: Chrysin enhances the inhibitory effect of VS4718 or Ponatinib on fatty acid metabolism in esophageal squamous cell carcinoma cell lines

[0063] After the KYSE450 cell line was placed in a 6-well plate, chrysin (12.5 μM) and / or VS4718 (0.5 μM) and ponatinib (0.5 μM) were added. One day later, the conditioned medium was collected for analysis of fatty acid release using a fatty acid detection kit (Nanjing Jiancheng Bioengineering Research Institute Co., Ltd., catalog number: A042-2-1). The conditioned medium under different treatments was incubated with different reagents according to the instructions of the reagent manual, and the fatty acid content in the conditioned medium was measured by measuring the absorbance value.

[0064] Compare with Figure 4 , the results showed that chrysin could enhance the inhibition of fatty acid metabolism of ESCC cell lines by VS4718 or ponatinib.

[0065] After calculation, the Q value for the fatty acid inhibition effect mediated by chrysin combined with VS4718 was 1.28; the Q value for the fatty acid inhibition effect mediated by chrysin combined with ponatinib was 1.18.

[0066] 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. A pharmaceutical composition comprising chrysin or a pharmaceutically acceptable salt thereof and a FAK inhibitor or a Src family kinase inhibitor; in, The FAK inhibitor includes VS4718 or a pharmaceutically acceptable salt thereof; the Src family kinase inhibitor includes ponatinib or a pharmaceutically acceptable salt thereof.

2. The pharmaceutical composition according to claim 1, characterized in that The molar ratio of chrysin or a pharmaceutically acceptable salt thereof to the FAK inhibitor or the Src family kinase inhibitor is 5-50:

1.

3. The pharmaceutical composition according to claim 1, characterized in that The molar ratio of chrysin or a pharmaceutically acceptable salt thereof to the FAK inhibitor or the Src family kinase inhibitor is 20-30:

1.

4. A kit comprising chrysin or a pharmaceutically acceptable salt thereof and a FAK inhibitor or a Src family kinase inhibitor; in, The FAK inhibitor includes VS4718 or a pharmaceutically acceptable salt thereof; the Src family kinase inhibitor includes ponatinib or a pharmaceutically acceptable salt thereof.

5. Use of the pharmaceutical composition according to any one of claims 1 to 3 in the preparation of a drug for treating esophageal squamous cell carcinoma.

6. The use according to claim 5, characterized in that: The treatment of esophageal squamous cell carcinoma includes inhibiting the growth of esophageal squamous cell carcinoma cells, inhibiting the invasion of esophageal squamous cell carcinoma cells in metastatic foci, inhibiting the sugar metabolism of esophageal squamous cell carcinoma cell lines, and inhibiting the fatty acid metabolism of esophageal squamous cell carcinoma cell lines.

7. The use according to claim 6, characterized in that: The esophageal squamous cell carcinoma cells include esophageal squamous cell carcinoma cell line KYSE410, esophageal squamous cell carcinoma cell line KYSE450, and esophageal squamous cell carcinoma cell line KYSE510.

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