Application of stiripentol in the preparation of anti-tumor drugs

Abstract

The present invention relates to the application of stiripentol in the preparation of anti-tumor drugs, and belongs to the field of biomedical technology. The present invention has found that stiripentol used for the treatment of epilepsy can reduce the activity of tumor cells such as non-small cell lung cancer, colorectal cancer, gastric cancer, etc., reduce tumor volume, prolong the survival time of tumor mice, and has a significant anti-tumor effect; stiripentol is used in combination with chemotherapy drugs, or in combination with radiotherapy, which can significantly enhance the anti-tumor effect, and stiripentol is used in combination with chemotherapy drugs or radiotherapy. There is a synergistic effect. The present invention has discovered a new use of stiripentol and expanded the application range of stiripentol. At the same time, stiripentol has good clinical safety and no toxic side effects, providing a new choice for clinical treatment drugs for tumors.

Description

Technical Field

[0001] The invention relates to the technical field of biomedicine, and in particular to the application of stiripentol in the preparation of anti-tumor drugs. Background Art

[0002] Stiripentol is a new drug for the treatment of epilepsy that was launched in 2007. Its chemical name is 4,4-dimethyl-1-(3,4-methylenedioxyphenyl)-1-penten-3-ol. French researchers reported that adding stiripentol (Siripanto) to sodium valproate and clobazam can effectively treat severe myoclonic epilepsy in infants and young children; stiripentol (Siripanto) is a cytochrome P450 inhibitor. When used in combination with clobazam and sodium valproate, stiripentol (Siripanto) has a therapeutic effect on severe myoclonic epilepsy (SMEI). The School of Medicine at Washington University in Missouri, USA, believes that it is difficult to determine whether stiripentol (Slipanto) reduces the frequency of epileptic seizures in patients in this combined drug experiment, because the mechanism of action of stiripentol (Slipanto) is to increase the blood concentration of other drugs such as clobazam and sodium valproate. The mechanism of action of stiripentol (Slipanto) is relatively unique. It can not only increase GABA release, but also inhibit the activity of certain enzymes, thereby increasing the blood concentration of other anti-epileptic drugs. Stiripentol (Slipanto) was approved in the European Union in 2001 for the adjuvant treatment of severe infantile epilepsy myoclonic seizures. Using stiripentol analogs, targeting lactate dehydrogenase can treat epilepsy, and energy metabolism can regulate the excitability of neurons, so special dietary treatments may inhibit drug-resistant epilepsy. Reported in the journal "Science" (DOI: 10.1126 / science.aaa129), studies have found that stiripentol, an anti-epileptic drug, is a lactate dehydrogenase A (LDHA) inhibitor. By modifying the chemical structure of stiripentol, the research team discovered a previously unknown LDH inhibitor that can effectively inhibit epilepsy in vivo. In summary, stiripentol analogs - LDH inhibitors are expected to become a new class of anti-epileptic drugs.

[0003] Lactate dehydrogenase (LDH) is a type of NAD-dependent kinase, a metalloprotein containing zinc ions, with a molecular weight of 135-140kD. It is one of the important enzyme systems for anaerobic glycolysis and gluconeogenesis, and can catalyze the reduction and oxidation reactions between pyruvate and L-lactic acid, as well as related α-keto acids. LDH is widely present in human tissues, with the highest content in the kidney, followed by myocardial and skeletal muscles.

[0004] LDHA is widely overexpressed in tumor tissues, including hematological malignancies and solid cancers. High expression of LDH-A provides many benefits to cancer cells, such as increased invasiveness and metastasis, as well as resistance to radiation and chemotherapy. In the past decade, many studies have observed the promoting role of LDHA in tumor cell metabolism, but the clinical application of LDH-A inhibitors as anticancer drugs remains unknown. Summary of the invention

[0005] The purpose of the present invention is to overcome the shortcomings of the prior art and provide the use of stiripentol in the preparation of anti-tumor drugs.

[0006] To achieve the above object, the technical solution adopted by the present invention is:

[0007] In a first aspect, the present invention provides the use of stiripentol in the preparation of anti-tumor drugs.

[0008] Through research, the present invention finds that stiripentol used to treat epilepsy can also reduce the survival percentage of tumor cells such as non-small cell lung cancer, colorectal cancer, and gastric cancer, can reduce the cell survival percentage of gastric cancer organoids, can reduce the tumor volume of gastric cancer tumor xenograft model mice, prolong the survival time of mice, and has a significant anti-tumor effect.

[0009] As a preferred embodiment of the application of the present invention, the tumor includes non-small cell lung cancer, colorectal cancer or gastric cancer.

[0010] In a second aspect, the present invention provides the use of stiripentol in the preparation of a drug for reducing and / or reversing tumor drug resistance.

[0011] The present invention has found through research that stiripentol can reduce the drug resistance of tumor cells such as non-small cell lung cancer, colorectal cancer, gastric cancer, etc. that are resistant to chemotherapy drugs (such as cisplatin).

[0012] As a preferred embodiment of the application of the present invention, the tumor includes non-small cell lung cancer, colorectal cancer or gastric cancer.

[0013] As a preferred embodiment of the application of the present invention, the chemotherapy drug is a DNA damaging chemotherapy drug.

[0014] As a preferred embodiment of the application of the present invention, the DNA damaging chemotherapy drugs include cisplatin, oxaliplatin, doxorubicin, fluorouracil or cyclophosphamide.

[0015] As a preferred embodiment of the application of the present invention, the tumor drug resistance refers to the resistance of the tumor to chemotherapy drugs.

[0016] In a third aspect, the present invention provides the use of stiripentol in preparing a drug for enhancing the effect of tumor radiotherapy.

[0017] The present invention has found through research that the combination of stiripentol and radiotherapy can significantly inhibit the tumor volume of tumor mice and significantly prolong the survival time of tumor mice. The combination of the two has a synergistic effect on the treatment of tumors and has a significant effect of enhancing the effect of tumor radiotherapy.

[0018] As a preferred embodiment of the application of the present invention, the radiotherapy method includes ionizing radiation, X-knife or gamma knife.

[0019] In a fourth aspect, the present invention provides the use of stiripentol in combination with a chemotherapeutic drug in the preparation of an anti-tumor drug.

[0020] The present invention has found through research that stiripentol can reverse the drug resistance of tumor cells to chemotherapy drugs, and the combination of stiripentol and chemotherapy drugs can significantly reduce the survival percentage of tumor cells, and has a more significant effect in treating tumors; compared with the use of stiripentol and chemotherapy drugs alone, the combination of stiripentol and chemotherapy drugs has a synergistic effect on the treatment of tumors.

[0021] As a preferred embodiment of the application of the present invention, the chemotherapy drug is a DNA damaging chemotherapy drug.

[0022] As a preferred embodiment of the application of the present invention, the DNA damaging chemotherapy drugs include cisplatin, oxaliplatin, doxorubicin, fluorouracil or cyclophosphamide.

[0023] As a preferred embodiment of the application of the present invention, the stiripentol is used in combination with a chemotherapeutic drug, and the amount of stiripentol used is 150 mg / kg / day.

[0024] In a fifth aspect, the present invention provides an anti-tumor combination drug, comprising stiripentol and a chemotherapeutic drug.

[0025] As a preferred embodiment of the application of the present invention, the chemotherapy drug is a DNA damaging chemotherapy drug.

[0026] As a preferred embodiment of the application of the present invention, the DNA damaging chemotherapy drugs include cisplatin, oxaliplatin, doxorubicin, fluorouracil or cyclophosphamide.

[0027] Compared with the prior art, the present invention has the following beneficial effects:

[0028] The present invention has found that stiripentol used to treat epilepsy can reduce the activity of tumor cells such as non-small cell lung cancer, colorectal cancer, and gastric cancer, reduce tumor volume, and prolong the survival time of tumor mice, and has a significant anti-tumor effect; stiripentol is used in combination with chemotherapy drugs, or in combination with radiotherapy, which can significantly enhance the anti-tumor effect, and stiripentol is used in combination with chemotherapy drugs or radiotherapy. There is a synergistic effect. The present invention has found a new use for stiripentol and expanded the application range of stiripentol. At the same time, stiripentol has good clinical safety and no toxic side effects, providing a new choice for clinical treatment drugs for tumors. BRIEF DESCRIPTION OF THE DRAWINGS

[0029] Figure 1 The cell viability and IC of each tumor cell line before and after treatment with cisplatin in Example 1 of the present invention are shown in Table 1. 50 result;

[0030] Figure 2 The results of the effects of stiripentol and cisplatin alone or in combination on the survival percentage of cisplatin-resistant tumor cell lines in Example 1 of the present invention;

[0031] Figure 3 The ATP activity test results of 5 organoids in Example 2 of the present invention;

[0032] Figure 4 The results of the effects of stiripentol and cisplatin alone or in combination on the cell survival percentage of cisplatin-resistant organoids in Example 2 of the present invention;

[0033] Figure 5 The results of the effects of stiripentol and cisplatin used alone or in combination on PDX-R model mice in Example 3 of the present invention; Control is a normal saline control group, Cisplatin is a cisplatin single treatment group, Stiripentol is a stiripentol single treatment group, and Stiripentol+Cisplatin is a stiripentol and cisplatin combined treatment group;

[0034] Figure 6 The results of the effects of stiripentol and ionizing radiation (IR) alone or in combination on PDX-R model mice in Example 3 of the present invention; wherein Control is a normal saline control group, IR is an ionizing radiation alone treatment group, Stiripentol is a stiripentol alone treatment group, and Stiripentol+IR is a stiripentol and ionizing radiation combined treatment group;

[0035] Figure 7The results are as follows: the effects of 4 LDHA inhibitors and cisplatin used alone or in combination on the survival percentage of PDX-R model mice in the comparative example of the present invention; wherein Control is a normal saline control group, Cisplatin is a cisplatin single treatment group, FX11 is an FX11 single treatment group, NHI-2 and NHI-2 single treatment groups, Quinoline-3-Sulfonamide is a 3-quinolinesulfonamide single treatment group, Oxamate is an oxamate single treatment group, Cisplatin+FX11 is a FX11 and cisplatin combined treatment group, Cisplatin+NHI-2 is a NHI-2 and cisplatin combined treatment group, Cisplatin+Quinoline-3-Sulfonamide is a 3-quinolinesulfonamide and cisplatin combined treatment group, and Cisplatin+Oxamate is an oxamate and cisplatin combined treatment group. DETAILED DESCRIPTION

[0036] In order to better illustrate the purpose, technical solutions and advantages of the present invention, the present invention will be further described below in conjunction with specific embodiments.

[0037] Unless otherwise specified, other materials, reagents, etc. used in the examples can be obtained from commercial sources.

[0038] Example 1 Effect of the combined use of stiripentol and cisplatin on the therapeutic effect of tumor cells

[0039] The efficacy of stiripentol combined with cisplatin was tested using a cisplatin (chemotherapeutic drug)-resistant tumor cell line model. The inventors first constructed a cisplatin-resistant tumor cell line using the drug concentration escalation method.

[0040] 1. Construction of cisplatin-resistant tumor cell lines

[0041] Tumor cell lines sensitive to the chemotherapy drug cisplatin were selected: non-small cell lung cancer cell line A549 (A549-P), colorectal cancer cell line HCT116 (HCT116-P), gastric cancer cell line AGS (AGS-P) and MGC803 cell line (MGC803-P), and the IC of each tumor cell line was tested. 50 Then, the tumor cell lines were plated on a 10 cm culture dish at a density of about 70-80%, and then cisplatin containing the IC 50 One tenth (10% IC 50 The cells were treated with medium (1640 medium + 10% FBS + double antibody) for 48 hours, and then replaced with medium without drugs for 48 hours; then the medium containing drugs and medium without drugs were repeatedly used for further culture, and the concentration of cisplatin in the medium containing drugs was gradually increased (20% IC 50 、40%IC 50、60%IC 50 、80%IC 50 、100%IC 50 、200%IC 50 、400%IC 50 ), the cisplatin treatment time was 6 months. After 6 months, the IC 50 The tumor cell lines after treatment with A549-P, HCT116-P, AGS-P and MGC803-P were denoted as A549-R, HCT116-R, AGS-R and MGC803-R, respectively.

[0042] Cell viability and IC of each tumor cell line before and after treatment with cisplatin 50 The results are as follows Figure 1 As shown, the results showed that the IC 50 All reached the IC of each tumor cell line before cisplatin treatment 50 The results showed that the cisplatin-resistant tumor cell line was successfully constructed. A549-R, HCT116-R, AGS-R and MGC803-R are all cisplatin-resistant tumor cell lines.

[0043] 2. Test of the efficacy of stiripentol combined with cisplatin on cisplatin-resistant tumor cell lines

[0044] The above-mentioned successfully constructed cisplatin-resistant tumor cell lines (A549-R, HCT116-R, AGS-R and MGC803-R) were used to test the therapeutic effects of stiripentol alone, cisplatin alone, and stiripentol combined with cisplatin.

[0045] A549-R, HCT116-R, AGS-R and MGC803-R were cultured in culture medium (1640 culture medium + 10% FBS + double antibody) containing different concentrations (0, 1, 5, 10, 20, 40, 80 μM) of stiripentol. After 48 h of culture, CCK-8 drug sensitivity experiment was performed, the absorbance was tested, and the cell survival percentage under each culture condition was calculated.

[0046] A549-R, HCT116-R, AGS-R and MGC803-R were cultured in culture medium (1640 culture medium + 10% FBS + double antibody) containing different concentrations (0, 10, 20, 40, 80, 120, 160 μM) of cisplatin. After 48 h of culture, CCK-8 drug sensitivity test was performed, the absorbance was tested, and the cell survival percentage under each culture condition was calculated.

[0047] Different concentrations of stiripentol and cisplatin were used together to culture A549-R, HCT116-R, AGS-R and MGC803-R, respectively. After 48 hours of culture, CCK-8 drug sensitivity test was performed, the absorbance was tested, and the cell survival percentage under each culture condition was calculated.

[0048] The results of the effects of stiripentol and cisplatin alone or in combination on the survival percentage of cisplatin-resistant tumor cell lines are as follows Figure 2 As shown, the results showed that stiripentol and cisplatin alone could significantly inhibit the survival of cisplatin-resistant tumor cell lines, and the cell survival percentage was significantly reduced, which had a significant tumor inhibitory effect and could reverse the cisplatin resistance of tumor cells; the combined use of stiripentol and cisplatin had a synergistic inhibitory effect on cisplatin-resistant tumor cell lines and could significantly reverse the cisplatin resistance of tumor cells.

[0049] Example 2 Effect of the combination of stiripentol and cisplatin on the therapeutic efficacy of organoid models derived from tumor patients

[0050] 1. Screening of cisplatin-resistant organoids

[0051] The inventors selected organoids from 5 gastric cancer patients from the Seventh Affiliated Hospital of Sun Yat-sen University, and named them PDO#1, PDO#2, PDO#3, PDO#4, and PDO#5. The 5 organoids were subcultured and inoculated into 96-well plates, and then cultured for 72 hours using cisplatin-containing culture medium (1640 culture medium + 10% FBS + double antibody), followed by ATP activity detection experiments. The effect of drugs on organoid activity was detected using the organoid drug sensitivity ATP activity detection method.

[0052] The results of ATP activity test of 5 organoids are as follows Figure 3 As shown, the results showed that the cell viability of organoids PDO#4 and PDO#5 treated with different concentrations of cisplatin was significantly higher than that of organoids PDO#1, PDO#2, and PDO#3, indicating that the cisplatin resistance of organoids PDO#4 and PDO#5 was significantly stronger than that of organoids PDO#1, PDO#2, and PDO#3. Organoids PDO#4 and PDO#5 are cisplatin-resistant organoids.

[0053] 2. Testing the efficacy of stiripentol combined with cisplatin on cisplatin-resistant organoids

[0054] The screened organoids PDO#4 and PDO#5 were used to test the therapeutic effects of stiripentol alone, cisplatin alone, and the combination of stiripentol and cisplatin, respectively.

[0055] Organoids PDO#4 and PDO#5 were cultured in culture medium (1640 culture medium + 10% FBS + double antibody) containing different concentrations (0, 5, 10, 20, 40, 80, 120 μM) of stiripentol. ATP activity detection experiments were performed after 72 hours of culture, the luminescence intensity was tested, and the cell survival percentage under each culture condition was calculated.

[0056] Organoids PDO#4 and PDO#5 were cultured in culture medium (1640 culture medium + 10% FBS + double antibody) containing different concentrations of cisplatin (0, 20, 40, 60, 80, 100, 120 μM). ATP activity detection experiments were performed after 72 hours of culture, the luminescence intensity was tested, and the cell survival percentage under each culture condition was calculated.

[0057] Different concentrations of stiripentol and cisplatin were used together to culture organoids PDO#4 and PDO#5, respectively. ATP activity detection experiments were performed after 72 hours of culture, the luminescence intensity was tested, and the cell survival percentage under each culture condition was calculated.

[0058] The results of the effects of stiripentol and cisplatin alone or in combination on the cell survival percentage of cisplatin-resistant organoids are shown in Figure 4 As shown, the results showed that stiripentol and cisplatin alone could significantly inhibit the survival of cisplatin-resistant organoids, and the cell survival percentage was significantly reduced, which had a significant inhibitory effect on tumor organoids and could reverse the cisplatin resistance of organoids; the combination of stiripentol and cisplatin had a synergistic inhibitory effect on cisplatin-resistant organoids and could significantly reverse the cisplatin resistance of organoids.

[0059] Example 3 Effect of stiripentol combined with cisplatin on the therapeutic efficacy of NSG mouse transplanted tumor model

[0060] The inventors collected fresh cisplatin-resistant tumor tissue from gastric cancer patients from the Seventh Affiliated Hospital of Sun Yat-sen University, transplanted the tumor tissue into immunodeficient mice (NSG mice), and then constructed a patient-derived tumor xenograft (PDX) model derived from gastric cancer patients; the cisplatin-resistant tumor tissue of gastric cancer patients, i.e., the patient-derived xenograft (PDX), was named PDX-R.

[0061] 1. Testing of the efficacy of stiripentol combined with cisplatin on PDX-R model

[0062] Fresh cisplatin-resistant tumor tissues collected from gastric cancer patients were transplanted into the back of NSG mice to obtain the PDX-R mouse model. Subsequently, stiripentol (150 mg / kg, once a day, 5 consecutive days a week) and cisplatin (2 mg / kg, once a week) were used for treatment alone or in combination (6 mice in each group). The tumor volume, survival percentage, and body weight of the mice were tested after different treatment times, and the ratio of the body weight after treatment to the body weight before treatment (body weight ratio) was calculated.

[0063] The effects of stiripentol and cisplatin alone or in combination on PDX-R model mice are shown in the following table. Figure 5 As shown, Control is the saline control group, Cisplatin is the cisplatin treatment group, Stiripentol is the stiripentol treatment group, and Stiripentol+Cisplatin is the stiripentol and cisplatin treatment group; the results show that stiripentol and cisplatin alone can inhibit the tumor volume of PDX-R model mice, significantly prolong the survival time of PDX-R model mice, and have a significant tumor inhibition effect; the combination of stiripentol and cisplatin has a synergistic effect on the inhibitory effect of cisplatin-resistant PDX-R model mice, which can more significantly inhibit tumor volume and prolong mouse survival time. There was no significant change in the weight of PDX-R model mice when stiripentol and cisplatin were used alone or in combination, indicating that stiripentol and cisplatin do not have serious toxic side effects on mice and have good safety.

[0064] 2. Testing the efficacy of stiripentol combined with ionizing radiation (IR) on PDX-R model

[0065] Combine stiripentol with radiotherapy such as ionizing radiation to study the therapeutic effect of stiripentol combined with radiotherapy on tumors.

[0066] Fresh cisplatin-resistant tumor tissues collected from gastric cancer patients were transplanted into the back of NSG mice to obtain the PDX-R mouse model, which was then treated with stiripentol (150 mg / kg, once a day for 5 consecutive days a week) and ionizing radiation (IR, 2 Gy each time, once a day for 4 consecutive days a week) alone or in combination (6 mice in each group). The tumor volume, survival percentage, and body weight of the mice were tested after different treatment times, and the ratio of the body weight after treatment to the body weight before treatment (body weight ratio) was calculated.

[0067] Effects of stiripentol and ionizing radiation (IR) alone or in combination on PDX-R model mice Figure 6As shown in the figure, Control is the normal saline control group, IR is the ionizing radiation alone treatment group, Stiripentol is the stiripentol alone treatment group, and Stiripentol+IR is the stiripentol and ionizing radiation combined treatment group; the results showed that stiripentol and ionizing radiation alone could inhibit the tumor volume of PDX-R model mice, significantly prolong the survival time of PDX-R model mice, and had a significant tumor inhibitory effect; the combined use of stiripentol and ionizing radiation had a synergistic effect on the inhibitory effect of cisplatin-resistant PDX-R model mice, which could more significantly inhibit the tumor volume and prolong the survival time of mice; there was no significant change in the body weight of PDX-R model mice when stiripentol and ionizing radiation were used alone or in combination, indicating that stiripentol and ionizing radiation would not cause serious toxic side effects on mice and had good safety.

[0068] The above NSG mouse transplant tumor model experiments showed that the combination of stiripentol and cisplatin can significantly reverse tumor cisplatin resistance and is safe.

[0069] Comparative test of the efficacy of different LDHA inhibitors combined with cisplatin on PDX-R model

[0070] The inventors selected four other LDHA inhibitors besides stiripentol: oxamate, FX11 (molecular formula C 22 H 22 O4), 3-quinolinesulfonamide (Quinoline-3-Sulfonamide), NHI-2 (C 17 H 12 F3NO3), respectively, were used in combination with cisplatin to test the therapeutic effects of different LDHA inhibitors combined with cisplatin on tumors. The tumor model used was the PDX-R model constructed in Example 3.

[0071] Fresh cisplatin-resistant tumor tissues from gastric cancer patients were transplanted into the back of NSG mice to obtain the PDX-R mouse model, which was then treated with the above four LDHA inhibitors and cisplatin alone or in combination (6 mice in each group), and the survival percentage of mice after different treatment times was tested. The doses of LDHA inhibitors and cisplatin treatment were: FX11 (50 mg / kg, once a day for 5 consecutive days a week), NHI-2 (25 mg / kg, once a day for 5 consecutive days a week), 3-quinolinesulfonamide (30 mg / kg, once a day for 5 consecutive days a week), oxamate (750 mg / kg; once a day), cisplatin (2 mg / kg, once a week).

[0072] The effects of 4 LDHA inhibitors and cisplatin alone or in combination on the survival percentage of PDX-R model mice are shown in the following table. Figure 7As shown, Control is the normal saline control group, Cisplatin is the cisplatin single treatment group, FX11 is the FX11 single treatment group, NHI-2 is the NHI-2 single treatment group, Quinoline-3-Sulfonamide is the 3-quinolinesulfonamide single treatment group, Oxamate is the oxamate single treatment group, Cisplatin+FX11 is the FX11 and cisplatin combined treatment group, Cisplatin+NHI-2 is the NHI-2 and cisplatin combined treatment group, Cisplatin+Quinoline-3-Sulfonamide is the 3-quinolinesulfonamide and cisplatin combined treatment group, Cisplatin+Oxamate is the oxamate and cisplatin combined treatment group;

[0073] The results showed that (1) the survival time of mice treated with FX11 alone and FX11 combined with cisplatin was significantly lower than that of the control group and the cisplatin alone group, indicating that FX11 alone could not effectively inhibit tumors, and the combination of FX11 and cisplatin could not effectively inhibit tumors, and there was no synergistic effect; the mice in the cisplatin alone group and the control group still survived at 30 days, and the lines corresponding to the survival percentages of the two groups overlapped;

[0074] (2) The survival time of mice treated with NHI-2 alone and NHI-2 combined with cisplatin was significantly lower than that of the control group and the cisplatin alone group, indicating that NHI-2 alone could not effectively inhibit tumors, and the combination of NHI-2 and cisplatin could not effectively inhibit tumors, and there was no synergistic effect; the mice in the cisplatin alone group and the control group still survived at 30 days, and the lines corresponding to the survival percentages of the two groups overlapped;

[0075] (3) The survival time of mice treated with 3-quinoline sulfonamide alone and 3-quinoline sulfonamide combined with cisplatin was significantly lower than that of the control group and the cisplatin group, indicating that 3-quinoline sulfonamide alone could not effectively inhibit tumors, and the combination of 3-quinoline sulfonamide and cisplatin could not effectively inhibit tumors, and there was no synergistic effect. Among them, the mice in the cisplatin group and the control group still survived at 30 days, and the corresponding lines of the survival percentages of the two groups overlapped;

[0076] (4) The survival time of mice treated with oxamate alone or oxamate combined with cisplatin was significantly lower than that of the control group and the cisplatin group, indicating that oxamate alone could not effectively inhibit tumors, and the combination of oxamate and cisplatin could not effectively inhibit tumors, and there was no synergistic effect. Among them, the mice in the cisplatin group and the control group were still alive at 30 days, and the corresponding lines of the survival percentages of the two groups overlapped.

[0077] In summary, the four LDHA inhibitors, oxamate, FX11, 3-quinolinesulfonamide and NHI-2, have serious toxic side effects, can cause rapid death of mice (all will cause death of mice within 20 days), significantly shorten the survival time of mice, have no obvious inhibitory effect on tumors, and have no obvious inhibitory effect on tumors when used in combination with the chemotherapy drug cisplatin, let alone synergistic effect. This shows that not all LDHA inhibitors have the effect of inhibiting tumors, and not all LDHA inhibitors and chemotherapy drugs have a synergistic effect of inhibiting tumors.

[0078] Finally, it should be noted that the above embodiments are only used to illustrate the technical solution of the present invention rather than to limit the scope of protection of the present invention. Although the present invention has been described in detail with reference to the preferred embodiments, those skilled in the art should understand that the technical solution of the present invention can be modified or replaced by equivalents without departing from the essence and scope of the technical solution of the present invention.

Claims

1. The use of stiripentol in the preparation of anti-tumor drugs, characterized in that: The tumor is non-small cell lung cancer, colorectal cancer or gastric cancer.

2. Use of stiripentol in the preparation of a drug for reducing and / or reversing tumor drug resistance, characterized in that: The tumor is non-small cell lung cancer, colorectal cancer or gastric cancer; the tumor drug resistance refers to the tumor's resistance to chemotherapy drugs; and the chemotherapy drug is cisplatin.

3. The use of stiripentol in the preparation of a drug for enhancing the effect of tumor radiotherapy, characterized in that: The tumor is non-small cell lung cancer, colorectal cancer or gastric cancer.

4. The use according to claim 3, characterized in that The radiotherapy methods include ionizing radiation, X-knife or gamma knife.

5. The use of stiripentol in combination with chemotherapy drugs in the preparation of anti-tumor drugs, characterized in that: The tumor is non-small cell lung cancer, colorectal cancer or gastric cancer; the chemotherapy drug is cisplatin.

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