Preventive and therapeutic drugs for tumors and their uses

Abstract

The present invention belongs to the pharmaceutical field and discloses a tumor preventive and therapeutic agent. In particular, it relates to the use of O6-methyl-2-deoxyguanosine-5-triphosphate (O6-methyl-dGTP) in the manufacture of a tumor preventive and / or therapeutic agent, and to a tumor preventive and / or therapeutic agent containing O6-methyl-dGTP. The present invention also relates to the use of O6-methyl-2-deoxyguanosine-5-triphosphate (O6-methyl-dGTP) in the manufacture of a tumor treatment, prevention, and / or control agent. The present invention unexpectedly discovered that O6-methyl-2-deoxyguanosine-5-triphosphate (O6-methyl-dGTP) significantly inhibits the growth and promotes apoptosis in various tumors, providing a novel candidate drug for tumor prevention and treatment. Animal experiments have demonstrated that O6-methyl-2-deoxyguanosine-5-triphosphate (O6-methyl-dGTP) has a clear tumor-inhibitory effect, making it highly likely to be industrially applicable and of great commercial and social value.

Description

[Technical Field]

[0001] The present invention belongs to the pharmaceutical field and relates to a preventive and therapeutic agent for tumors, and in particular to the use of O6-methyl-2-deoxyguanosine-5-triphosphate (O6-methyl-dGTP) in the manufacture of a drug for the treatment, prevention and / or control of tumors, and a preventive and therapeutic agent for tumors containing O6-methyl-dGTP. [Background technology]

[0002] Currently, chemotherapy remains the primary method of cancer treatment. Among numerous chemotherapeutic agents, alkylating agents were the first and still widely used anticancer drugs. The antitumor mechanism of alkylating agents is currently believed to be as follows: After spontaneous decomposition or enzymatic hydrolysis, active electrophiles are generated, which attack macromolecules such as DNA, generating a large number of alkylated DNA adducts. Compared with other products, O6-methylguanine (O6meG), which accounts for 8% of the modified amount, is sufficient to induce cell death and exert its antitumor cytotoxic effect.

[0003] Currently, research on alkylating agents focuses on the damage caused by O6-MedG on DNA strands and the subsequent cytotoxicity. However, it is worth noting that free nucleotides are approximately 190-13,000 times more sensitive to alkylation damage than nucleotides present in DNA strands. Helleday's team microinjected O6-methyl-dGTP into zebrafish embryos and found that the content of O6-methyl-dG on DNA strands significantly increased, which can cause embryonic toxicity in the presence of MTH1 inhibitors and / or MGMT inhibitors. The effect of O6-methyl-dGTP on tumor cells has not yet been reported.

[0004] Cancer is already the second leading cause of death worldwide. Although various new treatment methods, such as molecular targeted therapy and immunotherapy, have been developed, chemotherapy remains the main method of cancer treatment due to limitations in specific tumor types and treatment costs. Among the many chemotherapeutic drugs, alkylating agents were the first and still widely used anticancer drugs.

[0005] When alkylating agents interfere with cells or organisms, they can produce a large amount of alkylated DNA adducts. Compared to other products, O6-methylguanine (O6meG), accounting for 8% of the modification amount, is sufficient to cause cell death. O6MeG on DNA strands can match with T and induce G:C to A:T mutations. If O6MeG is removed by DNA mismatch repair (MMR), an ineffective mismatch repair cycle occurs, resulting in single- and double-strand breaks in DNA. If further repair is not possible, this can lead to activation of the apoptotic pathway and cell death. Living organisms have various mechanisms for repairing alkylated DNA damage, including methylguanine methyltransferase (MGMT), which can transfer a methyl group from the 6-position of guanine in DNA to a cysteine ​​residue in its active site, followed by its own degradation. Therefore, the expression level of MGMT in cells or tissues is closely related to the clinical therapeutic effect of alkylating agents. High MGMT expression levels in living organisms can lead to a certain degree of resistance to alkylating agent treatment. Therefore, there is an urgent need to explore the different mechanisms of action and resistance of alkylating agents and to develop new chemotherapeutic drugs.

[0006] Our previous research has shown that while current research on alkylating agents has focused on the damage caused by O6-MedG on DNA strands and the subsequent cytotoxicity, it is worth noting that free nucleotides are approximately 190-13,000 times more sensitive to alkylation damage than nucleotides present in DNA strands. Therefore, we believe that alkylating agents exert their effects by generating O6-methyl-dGTP.

[0007] Currently, there are few studies on the effects of O6-methyl-dGTP on cells or animals. Helleday's team only found that microinjecting O6-methyl-dGTP into zebrafish embryos significantly increased the content of O6-methyl-dG in DNA strands and could cause embryonic toxicity in the presence of MTH1 and / or MGMT inhibitors. There have been no reports on the effects of O6-methyl-dGTP on tumor cells and experimental animals. Therefore, we prepared O6-methyl-dGTP and used it to treat various tumor cells and tumor-bearing nude mice and mice. We found that O6-methyl-dGTP significantly reduced tumor cell viability, inhibited cell proliferation and tumor growth in tumor-bearing nude mice and mice, and promoted apoptosis, and these effects were unaffected by the expression level of MGMT. Therefore, O6-methyl-dGTP is superior to alkylating agents and has great medicinal and social value. Summary of the Invention [Problem to be solved by the invention]

[0008] The technical problem to be solved by the present invention is to provide a preventive and therapeutic agent for tumors and use thereof. [Means for solving the problem]

[0009] To achieve the above objectives, the present invention adopts the following technical solutions:

[0010] Use of O6-methyl-2-deoxyguanosine-5-triphosphate (O6-methyl-dGTP) in the manufacture of a medicament for the treatment, prevention and / or control of tumors.

[0011] The treatment, prevention and / or control of tumors may be one or more of the following: inhibiting tumor cell proliferation, preventing tumor development, or promoting tumor cell death.

[0012] Preferably, the tumor is a solid tumor or a hematological tumor.

[0013] Preferably, the tumor includes nervous system tumor, head and neck cancer, nasopharyngeal cancer, oral cancer, thyroid cancer, breast cancer, cervical cancer, uterine cancer, ovarian cancer, lung cancer, esophageal cancer, gastric cancer, colorectal cancer, liver cancer, pancreatic cancer, bladder cancer, kidney cancer, testicular cancer, prostate cancer, bone tumor, blood tumor, lymphoma, and late malignant tumor, inoperable malignant tumor, metastatic malignant tumor, etc.

[0014] An agent for the treatment, prevention, and / or control of tumors containing O6-methyl-2-deoxyguanosine-5-triphosphate (O6-methyl-dGTP).

[0015] The drug further comprises a biologically acceptable additive or carrier.

[0016] The drug may be an oral formulation, a parenteral formulation for injection, a nasal formulation, a transdermal formulation, a rectal formulation, or a depot formulation.

[0017] The oral preparations are tablets, capsules, cachets, soft capsules, solutions or suspensions; the parenteral injectable preparations are rapid intravenous injection preparations or continuous infusion preparations; the nasal mucosal preparations are aerosol preparations, sprays, mists or drops; the transdermal preparations are gels, ointments, sustained-release transdermal preparations, liposome preparations, transdermal patches or transdermal spray preparations; the rectal preparations are suppositories or retention enemas; and the depot preparations are subcutaneous or intramuscular implantation preparations or intramuscular injection preparations.

[0018] A method for treating, preventing, and / or controlling tumors, the method comprising administering to a mammal a therapeutically effective amount of O6-methyl-2-deoxyguanosine-5-triphosphate (O6-methyl-dGTP).

[0019] The therapeutically effective amount is 5 to 2000 μg / kg body weight, and preferably 200 to 1000 μg / kg body weight.

[0020] The tumors include nervous system tumors, head and neck cancer, nasopharyngeal cancer, oral cancer, thyroid cancer, breast cancer, cervical cancer, uterine cancer, ovarian cancer, lung cancer, esophageal cancer, gastric cancer, colorectal cancer, liver cancer, pancreatic cancer, bladder cancer, kidney cancer, testicular cancer, prostate cancer, bone tumors, blood tumors, lymphoma, and late malignant tumors, inoperable malignant tumors, metastatic malignant tumors, etc. [Effects of the Invention]

[0021] The advantages of the present invention are as follows: The present invention unexpectedly found that O6-methyl-dGTP significantly inhibits tumor growth and tumor cell proliferation in nude mice bearing various tumors, providing a novel candidate drug for tumor prevention and treatment. Furthermore, since the chemical synthesis method for O6-methyl-dGTP has been standardized, its clinical use is expected to have a bright future and is of great social value. [Brief explanation of the drawings]

[0022] Specific embodiments of the invention will now be described in more detail with reference to the drawings. [Figure 1] FIG. 1 shows the change in cell viability after interfering with cells of different origins with O6-methyl-dGTP. [Figure 2] FIG. 2 shows the changes in cell viability after interfering with different glioma cells with O6-methyl-dGTP. [Figure 3] FIG. 3 shows detection of the effect of O6-methyl-dGTP on the viability of HeLa cells after knocking down MGMT. [Figure 4] FIG. 4 shows that O6-methyl-dGTP blocks cell cycle progression. [Figure 5] FIG. 5 shows that cell apoptosis increases after interfering with tumor cells with O6-methyl-dGTP. [Figure 6A] FIG. 6A shows that O6-methyl-dGTP inhibits the growth of tumor mass in nude mice implanted with CT26 tumors. [Figure 6B]FIG. 6B shows that O6-methyl-dGTP and temozolomide inhibit the growth of tumor masses in nude mice xenografted with U251 tumors. [Figure 6C] FIG. 6C shows that O6-methyl-dGTP inhibits the growth of tumor mass in nude mice xenografted with Ln229 tumors. [Figure 7] FIG. 7 shows the change in cell viability after 24 hours of treatment of U251 cells with different concentrations of 8-oxodGTP and O6-methyl-dGTP. DETAILED DESCRIPTION OF THE INVENTION

[0023] Example 1: Drugs containing O6-methyl-dGTP 1. Experimental Materials (1) Active ingredient: O6-methyl-2-deoxyguanosine-5-triphosphate (O6-methyl-dGTP), synthesized by Tianjin Yaoming Kangde New Drug Development Co., Ltd.

[0024] (2) Drug carrier: Entranster™-in Vivo Reagent from Engreen Biosystem Co., Ltd., catalog number 18668-11, specification 1 mL, purchased from Beijing Engreen Biotechnology Co., Ltd., and Lipofectamine™ 3000 Infusion Reagent from Thermo Fisher Scientific, catalog number L3000001, specification 1.5 mL, purchased from Beijing Huashengjian Biotechnology Co., Ltd.

[0025] 2. Preparation method According to the instructions for use of the two drug carriers, an introduction complex was prepared with the active ingredient and drug carrier, among which the concentration of the active ingredient O6-methyl-2-deoxyguanosine-5-triphosphate (O6-methyl-dGTP) was 0.5 μg / μL, and the drug of the present invention was obtained.

[0026] Example 2: Cell experiments on tumor prevention and treatment 1. Experimental Materials (1) Experimental reagents: a) O6-methyl-dGTP injection: the drug obtained in Example 1. a) Blank carrier reagent: Prepared using the method of Example 1 using Thermo Fisher Scientific's Lipofectamine™ 3000 transfection reagent, with O6-methyl-2-deoxyguanosine-5-triphosphate (O6-methyl-dGTP) replaced with Opti-M to obtain a carrier solution containing no active ingredients.

[0027] c) Cell viability detection reagent: Promege's CellTiter-Glo® Luminescent Cell Viability Assay reagent, catalog number G7571, specifications 10 x 10 mL, purchased from Beijing Zhaosheng Laibo Trading Co., Ltd. The cell viability detection reagent was obtained by mixing the reagent to homogeneity according to the instruction manual.

[0028] e) Cell apoptosis detection reagent: Biyuntian Biotechnology Co., Ltd. Annexin V-FITC cell apoptosis detection kit, catalog number C1062M, purchased from Beijing Bainuowei Biotechnology Co., Ltd.

[0029] e) Cell cycle detection reagent: Cell cycle and cell apoptosis detection kit from Biyuntian Biotechnology Co., Ltd., catalog number C1052, purchased from Beijing Bainuowei Biotechnology Co., Ltd.

[0030] (2) Experimental cells: A549 and HCT116 were purchased from ATCC, MCF7, SW480, HepG2, and U251 were purchased from Beijing Union Cell Resource Center, and LN229 and U87MG were purchased from Beijing Xinsheng Technology Co., Ltd.

[0031] 2. Experimental Method (1) Detection of the effect of O6-methyl-dGTP on tumor cell viability 5×10 3The cells were seeded into a 96-well plate, attached to the wall, and allowed to grow for 24 hours. After that, different concentrations of O6-methyl-dGTP were introduced into the tumor cells using Lipofectamine™ 3000, followed by 48 hours of culture. The cell culture plate was left at room temperature for 30 minutes, and 100 μL of cell viability detection reagent was added to 100 μL of cell culture medium. The contents were mixed on an orbital shaker for 2 minutes to induce cell lysis. The culture plate was then incubated at room temperature for 10 minutes to stabilize the luminescence signal, which was then detected by the instrument and the signal value was recorded.

[0032] (2) Flow cytometry detection of the effect of O6-methyl-dGTP on tumor cell cycle 1×10 5 The cells were seeded into 24-well plates and allowed to adhere to the wells and grow for 24 hours. After 24 hours of growth, different concentrations of O6-methyl-dGTP were introduced into the tumor cells using Lipofectamine™ 3000 and cultured for 48 hours. The cells were collected, resuspended in approximately 1 mL of ice-cooled PBS, and transferred to a 1.5 mL centrifuge tube. The cells were then centrifuged again to precipitate the cells. The supernatant was carefully aspirated, and 1 mL of ice-cooled 70% ethanol was added. The cells were mixed uniformly by gentle pipetting. The cells were fixed at 4°C for 2 hours, stained with propidium iodide, and finally detected using a flow cytometer.

[0033] (3) Flow cytometry detection of the effect of O6-methyl-dGTP on tumor cell apoptosis 1×10 5Cells were seeded into 24-well plates and allowed to adhere to the wells and grow for 24 hours. After 24 hours, different concentrations of O6-methyl-dGTP were introduced into the tumor cells using Lipofectamine™ 3000 and subsequent culture for 48 hours. The cells were harvested, gently resuspended in PBS, and counted. 50,000–100,000 resuspended cells were removed and centrifuged at 1000×g for 5 minutes. The supernatant was discarded, and 195 μL of Annexin V-FITC conjugate was added to gently resuspend the cells. 5 μL of Annexin V-FITC was added, followed by 10 μL of propidium iodide staining solution, which was then gently mixed to homogenize. The cells were incubated for 10–20 minutes in the dark at room temperature and immediately detected by the instrument.

[0034] 3. Experimental Results (1) Inhibition of tumor cell growth by O6-methyl-dGTP As shown in Figures 1 and 2, after 48 hours of treatment of different types of tumor cells with different concentrations of O6-methyl-dGTP, the cell viability was significantly reduced in a dose-dependent manner, with the most obvious effect reaching nearly 90% inhibition after treatment with 200 μM O6-methyl-dGTP.

[0035] (2) The effect of O6-methyl-dGTP on tumor cells is independent of MGMT expression levels As shown in Figure 3, the effect of O6-methyl-dGTP on tumor cell viability was almost the same regardless of the level of MGMT expression.

[0036] (3) Blockade of tumor cell cycle progression by O6-methyl-dGTP As shown in Figure 4, after U251 cells were treated with different concentrations of O6-methyl-dGTP for 48 hours, the cell cycle was blocked in the S phase, and the proportion of cells in the S phase after treatment with 0.2 mM O6-methyl-dGTP was nearly 1-fold higher than that in the control group.

[0037] (4) Induction of apoptosis in tumor cells by O6-methyl-dGTP As shown in Figure 5, after 48 hours of treatment of U251 cells with different concentrations of O6-methyl-dGTP, cell apoptosis increased. The apoptotic cells in the 0.2 mM O6-methyl-dGTP group were more than two-fold higher than those in the control group, and the apoptotic cells in the 2 mM O6-methyl-dGTP group were more than six-fold higher than those in the control group. This indicates that O6-methyl-dGTP can induce apoptosis in tumor cells.

[0038] Example 3: Animal experiments on tumor prevention and treatment 1. Experimental Materials (1) Experimental reagents: a) O6-methyl-dGTP injection: the drug obtained in Example 1. (i) Blank carrier reagent: Prepared using the Entranster™-in Vivo reagent from Engreen Biosystem Co., Ltd. as described in Example 1, with O6-methyl-2-deoxyguanosine-5-triphosphate (O6-methyl-dGTP) replaced with pure water to create a carrier solution containing no active ingredients.

[0039] (2) Experimental animals: Balb / c male nude mice and mice, 17–19 g, 6 weeks old, purchased from Beijing Weitong Lihua Laboratory Animal Technology Co., Ltd.

[0040] All mice used in the experiment were kept in accordance with specific pathogen-free (SPF) animal care standards, with the room temperature limited to 20-26°C, humidity limited to 50-60%, and lighting alternating every 12 hours. Mice were fed sterilized standard diet and had free access to food and water.

[0041] (3) Experimental cells: CT26 cells and LN229 cells were purchased from ATCC, and U251 cells were purchased from the Peking Union Cell Resource Center.

[0042] 2. Experimental Method Tumor inoculation into nude mice, injection administration and dissection: (1) 1×10 6CT26 cells (200 μL) were subcutaneously inoculated into the back under the axilla of each mouse. After the tumor mass had grown to a predetermined size, the tumor mass was subcutaneously inoculated into 21 mice for a second time. The mice were randomly divided into a normal-fed group, a blank carrier control group, and an O6-methyl-dGTP group. The mice were administered the drug via the tail vein the day after the second inoculation. The O6-methyl-dGTP group received a dose of 2.5 mg / kg / injection, while the carrier control group received an equal amount of blank carrier reagent. A total of eight injections were given on days 0, 1, 2, 4, 6, 8, 10, and 12. After the injections were completed, the tumor mass was excised and weighed. The inhibition rate was calculated (inhibition rate = (1 - T 実験群 / C 対照群 )×100%).

[0043] (2) 1×10 7 Nude mice were subcutaneously inoculated with 200 μL of U251 cells near the back under the axilla. After the tumor mass reached a predetermined size, the tumor mass was inoculated a second time. After the tumor mass reached a predetermined size, the tumor mass was inoculated again. After the tumor mass reached a predetermined size again, the tumor mass was inoculated subcutaneously into the flank of 18 nude mice. When the tumor size exceeded 3 × 2 mm, the mice were randomly divided into a blank carrier control group, an O6-methyl-dGTP group, and a TMZ group. The mice were administered 2.5 mg / kg / injection of the O6-methyl-dGTP and TMZ groups, and the carrier control group received an equal amount of blank carrier reagent. A total of six injections were administered on days 0, 3, 6, 9, 12, and 15. After the injections were completed, the tumor masses were excised and weighed, and the inhibition rate was calculated (inhibition rate = (1 − T 実験群 / C 対照群 )×100%).

[0044] (3) 5 × 10 6Ln229 cells (200 μL) were subcutaneously inoculated into nude mice near the back under the axilla. After the tumor masses had grown to a predetermined size, the tumor masses were subcutaneously inoculated into 12 nude mice for a second time. When the tumor size exceeded 3 × 2 mm, the nude mice were randomly divided into a blank carrier control group and an O6-methyl-dGTP group, and administered via the tail vein. The O6-methyl-dGTP group received a dose of 2.5 mg / kg / injection, while the carrier control group received an equal amount of blank carrier reagent. A total of five injections were given on days 0, 2, 4, 6, and 8. After the injections were completed, the tumor masses were excised and weighed, and the inhibition rate was calculated (inhibition rate = (1 − T 実験群 / C 対照群 )×100%).

[0045] 3. Experimental Results Growth inhibition of tumor masses in nude mice and mice by O6-methyl-dGTP As shown in Table 1, Table 2, Table 3 and Figure 6A, Figure 6B, and Figure 6C, the inhibition rates of O6-methyl-dGTP against tumor xenografts derived from CT26, U251, and Ln229 were 41.32%, 68.77%, and 50.15%, respectively, compared with the vehicle control group. [Table 1] [Table 2] [Table 3]

[0046] 4. Experimental Conclusion The results of cell experiments and animal experiments showed that after administering O6-methyl-dGTP to interfere with tumors, cell growth was inhibited, apoptosis was increased, and tumor growth in nude mice and mice was slowed, demonstrating that O6-methyl-dGTP has the effect of inhibiting tumor growth and promoting apoptosis of tumor cells.

[0047] Example 4: Comparative Experiment 8-oxodGTP and O6-methyl-dGTP are two different small molecules, the most significant differences being that they modify bases at different sites, induce different types of mutations, involve different nucleic acid damage repair enzymes and repair mechanisms, and have different effects as tumor inhibitors.

[0048] 1. The base modification sites are different 8-oxo-dGTP is produced by oxidation of the C8 position of guanine, and O6-methyl-dGTP is produced by methylation of the O6 position of guanine.

[0049] (1) The structural formula of 8-oxodGTP is as follows: [ka]

[0050] (2) The structural formula of O6 methyl-dGTP is as follows: [ka]

[0051] 2. The types of mutations they cause are different 8-oxodGTP can be incorporated by DNA polymerase λ to match adenosine dA on the template, and it is incorporated opposite dA and dC with equal efficiency, causing A:T to C:G and G:C to T:A mutations, whereas O6-methyl-dGTP can be incorporated into the DNA strand to match dT, causing G:C to A:T mutations, and its matching preference with dT is 20 times higher than that with dC.

[0052] 3. The associated nucleic acid damage repair enzymes and repair mechanisms are different After 8-oxo-dGTP is incorporated into DNA, it matches with adenine (A) and cytosine (C) bases. Human 8-oxoguanine DNA glycosylase 1 (OGG1) preferentially recognizes and removes the 8-oxo-G that matches the C, initiating base excision repair (BER). Mammalian MutY homolog (MUTYH) removes the mismatched A and 8-oxo-G. If a C is subsequently incorporated opposite the 8-oxo-G, OGG1 can subsequently remove the 8-oxo-G that matches the C, resulting in ineffective base excision repair and strand breaks.

[0053] After being incorporated into the DNA strand, O6-methyl-dGTP can be removed by O6-methylguanine DNA methyltransferase (MGMT). If not repaired, O6meG:T is recognized by the mismatch repair system, the T is removed from the nascent strand, and if O6meG again matches with T in the next cycle, an ineffective mismatch repair cycle can occur, leading to DNA strand breaks.

[0054] 4. Different effects After 24 hours of treatment with 0.05 mM, 0.1 mM, 0.2 mM, and 2 mM 8-oxodGTP and O6-methyl-dGTP, respectively, U251 cells were incubated, and changes in cell viability were detected using the CellTiter-Glo® Luminescent Cell Viability Assay (Promega, G7571) kit.

[0055] The experimental method is as follows. 5×10 3The cells were seeded into a 96-well plate and allowed to adhere to the plate and grow for 24 hours. After that, different concentrations of 8-oxodGTP and O6-methyl-dGTP were transfected into U251 cells using Lipofectamine™ 3000 and cultured for another 24 hours. Reagents A and B of the CellTiter-Glo® Luminescent Cell Viability Assay (CTG) were mixed, and the 96-well plate was removed and left to equilibrate at room temperature for 30 minutes. Then, 100 μL of CTG reagent was added to each well. The plate was placed on a shaker for 2 minutes, and allowed to equilibrate in the dark for 10 minutes before detection. (CTG reagent was purchased from Promega, catalog number G7571.)

[0056] The results are shown in Figure 7. It can be seen that after the same concentration and the same time of interference, the inhibitory effect of O6 methyl-dGTP on U251 cells is obviously superior to that of 8-oxodGTP.

[0057] The several detailed descriptions provided above are merely specific examples of possible embodiments of the present invention, and are not intended to limit the scope of the present invention. Those skilled in the art will be able to design many other variations and embodiments, which fall within the principles and spirit of the present disclosure. More specifically, various modifications and improvements can be made to the components and / or structures of the thematic combinations within the scope of the disclosure, drawings, and claims of the present application. In addition to the modifications and improvements to the components and / or structures, other applications will be apparent to those skilled in the art.

Claims

1. A drug for treating, preventing and / or controlling a tumor, which drug contains O6-methyl-2-deoxyguanosine-5-triphosphate (O6-methyl-dGTP).

2. A drug for treating, preventing and / or controlling a tumor as described in claim 1, characterized in that the treatment, prevention and / or control of the tumor is one or more of the following uses: inhibiting the proliferation of tumor cells, preventing the development of tumors, or promoting tumor cell death.

3. A drug for treating, preventing and / or controlling a tumor as described in claim 1 or 2, characterized in that the tumor is a solid tumor or a blood tumor.

4. A drug for treating, preventing and / or controlling the tumor according to claim 3, characterized in that the tumor includes nervous system tumors, head and neck cancer, nasopharyngeal cancer, oral cancer, thyroid cancer, breast cancer, cervical cancer, uterine cancer, ovarian cancer, lung cancer, esophageal cancer, gastric cancer, colorectal cancer, liver cancer, pancreatic cancer, bladder cancer, kidney cancer, testicular cancer, prostate cancer, bone tumors, blood tumors, lymphoma, and late malignant tumors, unremovable malignant tumors, metastatic malignant tumors, etc.

5. The tumor treatment, prevention and / or control drug according to claim 1, characterized in that the tumor treatment, prevention and / or control drug further contains a biologically acceptable additive or carrier.

6. The tumor treatment, prevention and / or control drug described in claim 1 or 5, characterized in that the tumor treatment, prevention and / or control drug is an oral administration formulation, an injectable parenteral administration formulation, a nasal mucosal administration formulation, a transdermal administration formulation, a rectal administration formulation, or a depot preparation.

7. The drug for treating, preventing and / or controlling tumors according to claim 6, characterized in that the oral administration formulation is a tablet, capsule, cachet, soft capsule, solution or suspension, the parenteral administration formulation for injection is a rapid intravenous injection formulation or a continuous infusion formulation, the nasal administration formulation is an aerosol formulation, spray, mist or drops, the transdermal administration formulation is a gel, ointment, sustained-release transdermal administration formulation, liposome formulation, transdermal patch or transdermal spray formulation, the rectal administration formulation is a suppository or retention enema, and the depot preparation is a subcutaneous or intramuscular implantation formulation or an intramuscular injection formulation.

8. A drug for treating, preventing, and / or controlling tumors, comprising O6-methyl-2-deoxyguanosine-5-triphosphate (O6-methyl-dGTP), characterized in that a therapeutically effective amount of O6-methyl-2-deoxyguanosine-5-triphosphate (O6-methyl-dGTP) is administered to a mammal.

9. The drug for treating, preventing and / or controlling tumors according to claim 8, wherein the therapeutically effective amount is 5 to 2000 μg / kg body weight, preferably 200 to 1000 μg / kg body weight.

10. The tumor therapeutic, preventive and / or controlling drug according to claim 8 or 9, characterized in that the tumor includes nervous system tumors, head and neck cancer, nasopharyngeal cancer, oral cancer, thyroid cancer, breast cancer, cervical cancer, uterine cancer, ovarian cancer, lung cancer, esophageal cancer, gastric cancer, colorectal cancer, liver cancer, pancreatic cancer, bladder cancer, kidney cancer, testicular cancer, prostate cancer, bone tumors, blood tumors, lymphoma, and late malignant tumors, inoperable malignant tumors, metastatic malignant tumors, etc.

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