Application of pyruvate in preparation of lung cancer chemotherapy synergistic drug

Abstract

The invention belongs to the technical field of biological medicines, and particularly relates to application of pyruvate in preparation of a lung cancer chemotherapy synergistic medicine. The invention provides a novel medicine for treating lung cancer. The medicine is a compound I # imgabs0 # obtained after sodium pyruvate is subjected to structural improvement. Experimental results show that the compound can significantly inhibit the proliferation of lung cancer cells A549 in mice, has an inhibitory effect on the growth of nude mouse transplanted tumors of human lung cancer cells A549, expands the treatment potential of existing drugs, provides a new treatment choice for lung cancer patients, and has broad application prospects. The high efficiency of lung cancer treatment is of great significance in improving the treatment effect and relieving the burden of a patient.

Description

Technical Field

[0001] The invention belongs to the field of biomedicine technology, and in particular relates to the application of pyruvate in the preparation of lung cancer chemotherapy synergistic drugs. Background Art

[0002] With the rapid development of urbanization and the increasing aging of the population, the incidence and mortality of malignant tumors continue to increase worldwide. Lung cancer is the leading cause of cancer death in the world, seriously endangering human health.

[0003] Lung cancer is mainly divided into two histological types: non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). NSCLC accounts for about 85%, and SCLC accounts for about 15%. NSCLC cancer cells grow and divide slowly, and spread and metastasize relatively late. NSCLC can be further subdivided into adenocarcinoma, squamous cell carcinoma, adenosquamous carcinoma, large cell carcinoma, sarcomatoid carcinoma and other subtypes, mostly with local lung symptoms, such as cough, blood in sputum, chest pain, low fever, etc.; according to different stages, surgery, radiotherapy, chemotherapy, targeted, immune and other treatment methods can be applied; if it can be discovered and treated in time, the prognosis is relatively good. SCLC cancer cells are small, shaped like oatmeal particles, grow rapidly, are highly invasive, metastasize to distant sites early, have a high degree of malignancy, and are often related to smoking. In addition to lung symptoms, there may also be obvious systemic symptoms, such as abnormal secretion of antidiuretic hormone, Cushing's syndrome and other paraneoplastic syndromes; due to rapid growth and easy metastasis, they are often sensitive to radiotherapy and chemotherapy. However, metastasis often occurs when the diagnosis is confirmed, and the effect of surgical treatment is limited. Therefore, comprehensive radiotherapy and chemotherapy are the first choice for treatment. Obviously, chemoradiotherapy is an effective treatment for NSCLC and SCLC.

[0004] There are many kinds of chemical drugs used for lung cancer chemotherapy, such as cisplatin injection, paclitaxel injection, carboplatin injection, gemcitabine, pemetrexed disodium, ifosfamide, doxorubicin, vincristine, vinblastine and etoposide, which inhibit or kill lung cancer cells through different mechanisms. However, these drugs have great side effects when used in large quantities. For example, toxicity to the kidneys and gastrointestinal reactions may lead to renal tubular damage, increased blood urea nitrogen and serum creatinine levels; poor water solubility, traditional dosage forms require the use of hydrogenated castor oil and anhydrous ethanol as carriers, which may cause adverse reactions such as allergies, nephrotoxicity and neurotoxicity; multiple applications are prone to allergic reactions, and hypotensive shock may occur in severe cases; significant cardiotoxicity may lead to serious side effects such as abnormal electrocardiograms and arrhythmias.

[0005] Maximum tolerated dose chemotherapy (MTD) is the main form of traditional chemotherapy. Due to its severe toxic side effects, a 2-3 week interval is required after each cycle of chemotherapy to facilitate the recovery of the body's tissue and organ functions, which is prone to tumor resistance. In recent years, clinical tumor treatment has mostly adopted adjuvant chemoradiotherapy sensitization drugs for adjuvant therapy. The purpose is to maximize the killing effect and reduce the incidence of tumor resistance without increasing toxic effects. However, these drugs are expensive and have high adverse reactions after long-term use, resulting in poor patient compliance. Therefore, finding and developing new, highly effective and low-toxic lung cancer chemotherapy agents to reduce the dosage of chemotherapy is of great practical significance for the treatment of lung cancer and reversing / delaying lung cancer resistance. Summary of the invention

[0006] In order to overcome the deficiencies of the prior art, one of the objectives of the present invention is to provide the use of pyruvate in the preparation of a lung cancer chemotherapy synergist, thereby reducing the chemotherapy dosage while ensuring the chemotherapy effect.

[0007] One of the purposes of the present invention is achieved by the following technical solution: The use of pyruvate in the preparation of a lung cancer chemotherapy synergist, the structural formula of the pyruvate is as follows: .

[0008] Furthermore, the pyruvate is compound I, and the preparation process of compound I comprises the following steps: (1) Sodium pyruvate is added to an acetic acid solution of 4-bromo-o-phenylenediamine, and the mixture is reacted for 3 to 5 hours and then treated to obtain intermediate 2A; (2) 4-methoxy-α-bromoacetophenone, thiosemicarbazide and inorganic base were mixed evenly, subjected to microwave reaction at 190-205°C for 5-10 min, and then treated to obtain intermediate 1; (3) adding the intermediate 1 and 4-isothiocyanatophenol to a solvent in sequence, reacting under reflux for 2-3 hours, and then treating to obtain the intermediate 2; (4) The intermediate 2, the intermediate 2A, an inorganic base and copper powder are added to a solvent, subjected to microwave reaction at 150-170° C. for 25-35 min, and then treated to obtain compound I.

[0009] Furthermore, in step (1), the ratio of sodium pyruvate, 4-bromo-o-phenylenediamine, and acetic acid is 1 mmol: (1-1.25) mmol: (2-2.5) mL.

[0010] Furthermore, in step (2), the molar ratio of 4-methoxy-α-bromoacetophenone, thiosemicarbazide and inorganic base is 1:(1-1.5):(9-11).

[0011] Furthermore, in step (3), the molar ratio of the intermediate 1:4-isothiocyanatophenol is 1:(1-1.25).

[0012] Furthermore, in step (4), the molar ratio of the intermediate 2, intermediate 2A, inorganic base and copper powder is 1:(1-1.25):(2-3):(0.1-0.25).

[0013] Furthermore, the inorganic base in steps (2) and (4) is one of cesium carbonate and potassium carbonate.

[0014] Furthermore, the solvent in step (3) is one of toluene and xylene, and the solvent in step (4) is one of DMF and DMAC.

[0015] Furthermore, the compound I is used to prepare a drug for treating lung cancer.

[0016] Furthermore, the medicine also includes pharmaceutically acceptable excipients.

[0017] Furthermore, the power of the microwave reaction in steps (2) and (4) is 800 W and the frequency is 2500 Hz.

[0018] Compared with the prior art, the present invention has the following beneficial effects: The present invention obtains a pyruvate derivative compound I with higher anti-cancer activity by chemically modifying the pyruvate molecule. The compound can inhibit half of the A549 lung cancer cells at a lower concentration (0.287 μM), and can inhibit the epithelial-mesenchymal transition (EMT) process, and at the same time has an inhibitory effect on the growth of nude mouse transplanted tumors of human lung cancer A549 cells. BRIEF DESCRIPTION OF THE DRAWINGS

[0019] Figure 1 This is the synthetic route of compound I of the present invention; Figure 2 Schematic diagram of the effect of compound Ⅰ of the present invention on A549 lung cancer cells; Figure 3 This is a schematic diagram of the effect of compound I of the present invention on E-cadherin in the cell EMT process; Figure 4 This is a schematic diagram of the effect of compound I of the present invention on Vimentin in the cell EMT process; Figure 5This is a schematic diagram of the effect of compound I of the present invention on Fibronectin in the cell EMT process; Figure 6 This is a schematic diagram of the effect of compound Ⅰ of the present invention on N-cadherin in the cell EMT process. DETAILED DESCRIPTION

[0020] Below, in conjunction with the accompanying drawings and specific embodiments, the present invention is further described. It should be noted that, under the premise of no conflict, the embodiments described below or the technical features can be arbitrarily combined to form new embodiments. The specific conditions not specified in the embodiments are carried out according to conventional conditions or conditions recommended by the manufacturer. The reagents or instruments used, unless otherwise specified, are conventional products obtained through commercial channels.

[0021] Example 1 The use of pyruvate in the preparation of a lung cancer chemotherapy synergist, wherein the pyruvate is compound I, and the structural formula of compound I is as follows: .

[0022] The synthetic route of compound I is as follows Figure 1 As shown, the following steps are included: (1) 4-Bromo-o-phenylenediamine (20 mmol) was placed in 50 mL of acetic acid, and then sodium pyruvate (20 mmol) was dissolved in 9 mL of deionized water. The sodium pyruvate solution was added dropwise to the 4-bromo-o-phenylenediamine solution under stirring. The mixture was reacted at room temperature for 3 h. The reaction solution was filtered, and the filter cake was washed with deionized water and then dried to obtain intermediate 2A.

[0023] Intermediate 2A 1 H NMR (C9H7N2OBr, 400MHz, DMSO-d6) δ: 10.68 (s, 1H), 7.54-7.47 (m, 3H), 2.07 (s, 3H); [M+H] + m / z: 238.97, ESI-MS (m / z): 239.30. 1 The results of HNMR and MS confirmed that it was the target product.

[0024] (2) 4-Methoxy-α-bromoacetophenone (10 mmol) and semicarbazide (10 mmol) were added to a microwave reactor (800 W, 2500 Hz), and then potassium carbonate (0.11 mol) was added, and the reaction was carried out at 200°C for 5 min. After cooling to room temperature, sufficient water was added to dilute the reaction solution, and the reaction solution was filtered to obtain a filter cake. The filter cake was slurried with methanol and then dried to obtain intermediate 1.

[0025] Intermediate 1 1H NMR (C 10 H 11 N3OS, 400MHz, DMSO-d6) δ: 9.30 (s, 2H), 7.94 (d, 2H), 7.08 (d, 2H), 3.83 (s, 3H), 3.72 (s, 2H); [M+H] + m / z: 222.06, ESI-MS (m / z): 222.16. 1 The results of HNMR and MS confirmed that it was the target product.

[0026] (3) Intermediate 1 (20 mmol) and 4-isothiocyanatophenol (20 mmol) were added to 50 mL of toluene and refluxed in toluene for 2 h. After the reaction, the system was cooled to room temperature and filtered to obtain a filter cake. The filter cake was washed with toluene and n-hexane in turn, and then slurried with ethanol and dried to obtain intermediate 2.

[0027] Intermediate 2 1 H NMR (C 17 H 16 N4O2S2, 400MHz, DMSO-d6) δ: 12.24 (s, 1H), 10.96 (s, 1H), 9.42 (s, 1H), 7.94 (d ,2H), 7.27 (d,2H), 7.08 (d,2H), 6.72 (d,2H), 3.83 (s,3H), 3.72 (s,2H); [M+H] + m / z: 373.07, ESI-MS (m / z): 373.12. 1 The results of HNMR and MS confirmed that it was the target product.

[0028] (4) Intermediate 2A (6 mmol) and intermediate 2 (5 mmol) were added to 6 mL of N,N-dimethylformamide (DMF), potassium carbonate (10 mmol) and copper powder (1.25 mmol) were added as catalysts, and the mixture was reacted at 150 °C for 30 min in a microwave reactor (800 W, 2500 Hz). After the reaction was completed, the mixture was cooled to room temperature, and then the reaction was quenched with water. The organic layer was extracted with ethyl acetate and then dried and passed through a column to obtain compound I.

[0029] Compound I 1 H NMR (C 26 H 22N6O3S2, 400MHz, DMSO-d6) δ: 12.24 (s, 1H), 10.96 (s, 1H), 10.68 (s, 1H), 7.94 (d, 2 H), 7.41 (d, 2H), 7.20-7.16 (d, 7H), 3.83 (s, 3H), 3.72 (s, 2H), 2.07 (s, 3H); [M+H] + m / z: 531.12, ESI-MS (m / z): 531.12. 1 The results of HNMR and MS confirmed that it was the target product.

[0030] Example 2 A use of pyruvate in the preparation of a lung cancer chemotherapy synergist, wherein the pyruvate is compound I, and the preparation process of compound I comprises the following steps: (1) 4-Bromo-o-phenylenediamine (25 mmol) was placed in 40 mL of acetic acid, and then sodium pyruvate (20 mmol) was dissolved in 15 mL of deionized water. Then, the sodium pyruvate was added dropwise to the 4-bromo-o-phenylenediamine solution under stirring. The mixture was reacted at room temperature for 4 h. The reaction solution was filtered, and the filter cake was washed with deionized water and then dried to obtain intermediate 2A.

[0031] (2) 4-Methoxy-α-bromoacetophenone (10 mmol) and semicarbazide (15 mmol) were added to a microwave reactor (800 W, 2500 Hz), and then cesium carbonate (0.1 mol) was added, and the reaction was carried out at 190° C. for 10 min. After cooling to room temperature, sufficient water was added to dilute the reaction solution, and the reaction solution was filtered to obtain a filter cake. The filter cake was slurried with methanol and then dried to obtain intermediate 1.

[0032] (3) Intermediate 1 (20 mmol) and 4-isothiocyanatophenol (25 mmol) were added to 50 mL of xylene and refluxed in xylene for 3 h. After the reaction, the system was cooled to room temperature and filtered to obtain a filter cake. The filter cake was washed with xylene and n-hexane in turn, and then slurried with ethanol and dried to obtain intermediate 2. 1 The results of HNMR and MS were consistent with those of Example 1.

[0033] (4) Intermediate 2A (5 mmol) and intermediate 2 (5 mmol) were added to 6 mL of N,N-dimethylacetamide (DMAC), and cesium carbonate (15 mmol) and copper powder (1 mmol) were added as catalysts. The mixture was reacted at 170 °C for 25 min in a microwave reactor (800 W, 2500 Hz). After the reaction was completed, the mixture was cooled to room temperature, and then the reaction was quenched with water. The organic layer was extracted with ethyl acetate and then dried and passed through a column to obtain compound I. 1 The results of HNMR and MS were consistent with those of Example 1.

[0034] Example 3 A use of pyruvate in the preparation of a lung cancer chemotherapy synergist, wherein the pyruvate is compound I, and the preparation process of compound I comprises the following steps: (1) 4-Bromo-o-phenylenediamine (23 mmol) was placed in 45 mL of acetic acid, and then sodium pyruvate (20 mmol) was dissolved in 22 mL of deionized water. Then, the sodium pyruvate was added dropwise to the 4-bromo-o-phenylenediamine solution under stirring. The mixture was reacted at room temperature for 5 h. The reaction solution was filtered, and the filter cake was washed with deionized water and then dried to obtain intermediate 2A.

[0035] (2) 4-Methoxy-α-bromoacetophenone (10 mmol) and semicarbazide (12 mmol) were added to a microwave reactor (800 W, 2500 Hz), and then potassium carbonate (0.09 mol) was added. The mixture was reacted at 205° C. for 8 min. After cooling to room temperature, sufficient water was added to dilute the reaction solution, and the reaction solution was filtered to obtain a filter cake. The filter cake was slurried with methanol and then dried to obtain intermediate 1.

[0036] (3) Intermediate 1 (20 mmol) and 4-isothiocyanatophenol (22 mmol) were added to 40 mL of toluene and refluxed in toluene for 2.5 h. After the reaction, the system was cooled to room temperature and filtered to obtain a filter cake. The filter cake was washed with toluene and n-hexane in turn, and then slurried with ethanol and dried to obtain intermediate 2. 1 The results of HNMR and MS were consistent with those of Example 1.

[0037] (4) Intermediate 2A (5.5 mmol) and intermediate 2 (5 mmol) were added to 6 mL of N,N-dimethylformamide (DMF), potassium carbonate (12 mmol) and copper powder (0.5 mmol) were added as catalysts, and the mixture was reacted at 160 °C for 35 min in a microwave reactor (800 W, 2500 Hz). After the reaction was completed, the mixture was cooled to room temperature, and then the reaction was quenched with water, extracted with ethyl acetate to obtain an organic layer, which was then dried and passed through a column to obtain compound I. 1 The results of HNMR and MS were consistent with those of Example 1.

[0038] Test Example 1 Cytotoxicity of Compound I of the present invention on A549 lung cancer cells Adjust the concentration of A549 lung cancer cell suspension in the logarithmic growth phase to 5×10 4 / mL, centrifuge and mix to form a single cell suspension, add 100μL to each well of a 96-well culture plate, and culture in a 37°C, 5% CO2 incubator until the cells are 80% confluent, then add drugs. Add 100μL of compound Ⅰ (0.05, 0.10, 0.25, 0.30, 0.50μM) and DMSO (negative control) of Example 1 to each well and stimulate for 24h. Add 20μL of MTT (5mg / mL) solution to each well and continue incubating in the cell culture incubator for 4 hours. Use an enzyme marker to measure the absorbance OD value of each well at a wavelength of 490nm. This experiment was repeated three times, and the experimental results are as follows Figure 2 shown.

[0039] Depend on Figure 2 It can be seen that compound I prepared by the present invention can significantly inhibit the proliferation of lung cancer cells A549, and its IC 50 =0.287 μM, which indicates that compound Ⅰ has a high inhibitory effect on lung cancer cells A549.

[0040] Test Example 2 Effect of Compound I of the present invention on inhibiting EMT of A549 lung cancer cells Epithelial-mesenchymal transition (EMT) is a complex cellular process in which cancer cells lose apical-basal polarity and cell-cell adhesion (both characteristics of epithelial cells) and acquire the characteristics of mesenchymal cells. Mesenchymal cells that have acquired new mobility can migrate from the primary tumor site and spread to secondary sites. Compound I inhibits the EMT process of alveolar epithelial cells, thereby inhibiting the migration and invasion of lung cancer cells. EMT is characterized by the loss of epithelial cell markers and the upregulation of mesenchymal cell markers. In order to investigate the effect of compound I on cell EMT. The EMT model of lung cancer cells A549 was established by stimulating TGF-β. The specific steps of the inhibition of cell EMT by compound I are as follows: (1) Non-small cell lung cancer A549 cells in the logarithmic growth phase were digested with trypsin, centrifuged, resuspended, and counted. 5 / mL was inoculated into a 24-well plate, and 500 μL was added to each well; (2) After the cells adhered, starve the cells with EMEM medium containing 0.5% FBS for 12 h; (3) Prepare a 5 ng / mL TGF-β solution using EMEM medium containing 0.5% FBS as the TGF-β group; dissolve the compound I of the present invention in DMSO to prepare a 100 mM compound I solution. Dilute the compound I solution to the corresponding concentration (TGF-β+20 nM compound I, TGF-β+50 nM compound I, TGF-β+100 nM compound I) using a medium containing 5 ng / mL TGF-β. Use the medium without TGF-β as the blank control group; (4) Finally, remove the medium used for starving cells and add the diluted compound into the wells. After 24 hours of incubation, wash once with PBS and add 200 μL Trizol to lyse and collect RNA samples; (5) RNA transcription was performed using the PrimeScript RT Master Mix Kit, and then real-time fluorescence quantitative PCR detection was performed using the 2×SYBRGreen qPCR Master Mix Kit. Figure 3-6 shown.

[0041] Depend on Figure 3-6 It can be seen that the transcriptional expression level of the epithelial marker E-cadherin in A549 cells exposed to TGF-β was reduced, and the transcriptional expression levels of mesenchymal cell markers Vimentin, Fibronectin and N-cadherin were high. After treatment with compound I, the transcriptional expression level of epithelial markers was significantly increased and the transcriptional level of mesenchymal cell markers was inhibited, indicating that compound I can inhibit the EMT process and has the ability to inhibit the migration and invasion of lung cancer cells.

[0042] Test Example 3 Effect of Compound Ⅰ of the present invention on the growth of lung cancer A549 cell transplanted tumor in nude mice (1) Preparation of nude mouse non-small cell lung cancer A549 cell transplant tumor model 40 SPF BALB / c-nu mice, 6 weeks old, weighing 16-18 g. Take A549 cells of lung cancer cell line in logarithmic growth phase, and adjust the concentration of A549 cells to 3×10 7 A549 cells (0.1 mL) were inoculated subcutaneously on the back of BALB / c-nu mice. 3 When , the model is constructed successfully.

[0043] (2) Trial groups and medication methods The mice with successful modeling were randomly divided into the following 3 groups, with 12 mice in each group, and the drugs were administered starting from the second day after successful modeling: Example group: Compound I prepared in Example 1 was administered by gavage at a dose of 25 mg Compound I / kg / d, once / day, for 14 consecutive days; Gefitinib group: gefitinib was administered by gavage at a dose of 25 mg / kg / d, once a day, for 14 consecutive days; Model control group: gavage with an equal amount of normal saline once a day for 14 consecutive days.

[0044] 48 hours after the last administration, mice were killed by dislocation, transplanted tumors were removed, and tumor weight was measured. Tumor weight inhibition rate (%) = (1-mean tumor weight of the experimental group / mean tumor weight of the model control group) × 100%. The effect of the drug on the inhibition of tumor growth in nude mice with human lung cancer A549 cells was reflected by comparing tumor weight. Data are presented as mean ± standard deviation SPSS 15.0 software was used for variance analysis.

[0045] (3) Results and analysis The test results are shown in Table 1.

[0046] Table 1 Tumor weight inhibition rate of compound I of the present invention and gefitinib on lung cancer As can be seen from Table 1, the compound I prepared by the present invention has an inhibitory effect on the growth of human lung cancer A549 cell nude mouse transplanted tumors. Compared with the gefitinib group, the average tumor inhibition rate is improved, which shows that the compound I of the present invention is highly effective in treating lung cancer, and can achieve highly effective tumor inhibition with a smaller dose of the drug, thereby obtaining an unexpected technical effect.

[0047] In summary, the compound I prepared by the present invention can significantly inhibit the proliferation of lung cancer cells A549 in mice, and also has an inhibitory effect on the growth of human lung cancer A549 cell transplanted tumors in nude mice, has excellent clinical application prospects, and provides a new and effective medication route for the treatment of lung cancer.

[0048] The above-mentioned embodiments are only preferred embodiments of the present invention and cannot be used to limit the scope of protection of the present invention. Any non-substantial changes and substitutions made by technicians in this field on the basis of the present invention shall fall within the scope of protection required by the present invention.

Claims

1. The use of pyruvate in the preparation of a lung cancer chemotherapy synergist, characterized in that: The structural formula of the pyruvate is shown below: 。 2. The use of pyruvate according to claim 1 in the preparation of a lung cancer chemotherapy synergist, characterized in that: The pyruvate is compound I, and the preparation process of compound I comprises the following steps: (1) Sodium pyruvate is added to an acetic acid solution of 4-bromo-o-phenylenediamine, and the mixture is reacted for 3 to 5 hours and then treated to obtain intermediate 2A; (2) 4-methoxy-α-bromoacetophenone, thiosemicarbazide and inorganic base were mixed evenly, subjected to microwave reaction at 190-205°C for 5-10 min, and then treated to obtain intermediate 1; (3) adding the intermediate 1 and 4-isothiocyanatophenol to a solvent in sequence, reacting under reflux for 2-3 hours, and then treating to obtain the intermediate 2; (4) The intermediate 2, the intermediate 2A, an inorganic base and copper powder are added to a solvent, subjected to microwave reaction at 150-170° C. for 25-35 min, and then treated to obtain compound I.

3. The use of pyruvate according to claim 2 in the preparation of a lung cancer chemotherapy synergist, characterized in that: The dosage ratio of sodium pyruvate, 4-bromo-o-phenylenediamine and acetic acid in step (1) is 1 mmol: (1-1.25) mmol: (2-2.5) mL.

4. The use of pyruvate according to claim 2 in the preparation of a lung cancer chemotherapy synergist, characterized in that: The molar ratio of 4-methoxy-α-bromoacetophenone, thiosemicarbazide and inorganic base in step (2) is 1:(1-1.5):(9-11).

5. The use of pyruvate according to claim 2 in the preparation of a lung cancer chemotherapy synergist, characterized in that: The molar ratio of the intermediate 1 and 4-isothiocyanatophenol in step (3) is 1:(1-1.25).

6. The use of pyruvate according to claim 2 in the preparation of a lung cancer chemotherapy synergist, characterized in that: The molar ratio of the intermediate 2, intermediate 2A, inorganic base and copper powder in step (4) is 1: (1-1.25): (2-3): (0.1-0.25).

7. The use of pyruvate according to claim 2 in the preparation of a lung cancer chemotherapy synergist, characterized in that: The inorganic base in steps (2) and (4) is one of cesium carbonate and potassium carbonate.

8. The use of pyruvate according to claim 2 in the preparation of a lung cancer chemotherapy synergist, characterized in that: The solvent in step (3) is one of toluene and xylene, and the solvent in step (4) is one of DMF and DMAC.

9. The use of pyruvate according to claim 2 in the preparation of a lung cancer chemotherapy synergist, characterized in that: The compound I is used to prepare medicine for treating lung cancer.

10. The use of pyruvate according to claim 9 in the preparation of a lung cancer chemotherapy synergist, characterized in that: The drug also includes pharmaceutically acceptable excipients.

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