Pharmaceutical composition for treating triple-negative breast cancer

Abstract

The objective of the present invention is to provide a pharmaceutical composition for treating triple-negative breast cancer, which contains actinomycin and doxorubicin as active ingredients. [Solution] The pharmaceutical composition of the present invention can target and bind to a specific nucleic acid sequence due to the synergistic effect of actinomycin and doxorubicin, and therefore can suppress or treat triple-negative breast cancer while reducing the dosage of doxorubicin, and can effectively reduce the side effects of chemotherapy drugs.

Description

[Technical Field]

[0001] The present invention relates to a pharmaceutical composition, and in particular to a pharmaceutical composition for treating triple-negative breast cancer. [Background technology]

[0002] The World Health Organization (WHO) points out that breast cancer is the most common cancer among women, and that triple-negative breast cancer (TNBC) has the highest mortality rate. Triple-negative breast cancer is breast cancer that is negative for three hormone receptors: estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor type 2 (HER2). Patients have limited treatment options, and because triple-negative breast cancer is highly prone to genetic mutations, it has a high recurrence rate even after treatment and a poor prognosis. For this reason, how to treat triple-negative breast cancer has been a major challenge in clinical practice for many years.

[0003] Because triple-negative breast cancer patients lack the three receptors mentioned above, hormone therapy and molecular targeted therapy cannot be used as treatment methods, and chemotherapy remains the primary treatment. However, chemotherapy drugs not only have side effects, but also have a maximum cumulative dose. In other words, once the maximum cumulative dose is reached, continued use of the drug is not recommended. Furthermore, concerns about cardiotoxicity and weakened immunity have narrowed the treatment options for patients. For example, doxorubicin, the chemotherapy drug most commonly used in clinical settings to treat triple-negative breast cancer, has a lifetime cumulative dose limit of 550 mg / m. 2 (body surface area), and the recommended dose of doxorubicin monotherapy for triple-negative breast cancer is 60-75 mg / m 2It is administered once every three weeks, and the recommended dose in combination with other chemotherapy drugs is 40-75 mg / m2, administered once every three to four weeks. Therefore, the number of lifetime doxorubicin treatments a patient can receive is limited. In addition to chemotherapy, immunotherapy is currently attracting attention as a new treatment for triple-negative breast cancer. However, immunotherapy is not suitable for all triple-negative breast cancer patients, and due to its high cost, it is not available to all patients. Summary of the Invention [Problem to be solved by the invention]

[0004] In order to solve the above problems, the main object of the present invention is to provide a pharmaceutical composition for treating triple-negative breast cancer, which can reduce the dosage of known chemotherapeutic drugs, alleviate the side effects of the drugs, and improve the prognosis in triple-negative breast cancer patients.

[0005] Another object of the present invention is to provide a pharmaceutical composition for treating triple-negative breast cancer, which can delay the onset of disease caused by the accumulation of chemotherapy drugs in the body and extend the period during which patients can use chemotherapy drugs. [Means for solving the problem]

[0006] To achieve the above objectives, the present invention provides a use of a chemotherapeutic agent for preparing a pharmaceutical composition for treating triple-negative breast cancer and metastasis. The chemotherapeutic agent comprises actinomycin D and doxorubicin. By administering an effective amount of the pharmaceutical composition containing actinomycin D and doxorubicin to a patient with triple-negative breast cancer, actinomycin D and doxorubicin are intercalated into the GCCG sequence, allowing the pharmaceutical composition to bind to a nucleic acid molecule containing the GCCG sequence, thereby suppressing the proliferation and metastasis of triple-negative breast cancer cells and achieving a therapeutic effect on triple-negative breast cancer.

[0007] The pharmaceutical composition for treating triple-negative breast cancer consists of actinomycin D and doxorubicin.

[0008] In one embodiment of the present invention, the effective amount in the pharmaceutical composition means that the dosage ratio of actinomycin D to doxorubicin is 1:100 to 1:600.

[0009] In another embodiment of the present invention, when the subject of administration is a human, the effective amount in the pharmaceutical composition is preferably such that the dosage ratio of actinomycin D to doxorubicin is 1:10 to 1:30, and the combination ratio of actinomycin D to doxorubicin is 1:25.

[0010] In another embodiment of the present invention, the present invention provides the use of a chemotherapeutic agent in the preparation of a nucleic acid intercalator. The chemotherapeutic agent comprises actinomycin D and doxorubicin, and the nucleic acid intercalator is used to bind to the GCCG sequence in a nucleic acid molecule. Specifically, by administering an effective amount of the nucleic acid intercalator to an individual, actinomycin D and doxorubicin are intercalated into the GCCG sequence, and the nucleic acid intercalator and the nucleic acid molecule containing the GCCG sequence are bound to form a complex, which can affect the normal function of the nucleic acid molecule containing the GCCG sequence or the cells containing the nucleic acid molecule.

[0011] The dosage ratio of actinomycin D to doxorubicin is 1:100 to 1:600.

[0012] When the subject of administration is a human, the compounding ratio of actinomycin D to the doxorubicin is preferably 1:10 to 1:30, and the compounding ratio of actinomycin D to the doxorubicin is 1:25. [Effects of the Invention]

[0013] The present invention provides a pharmaceutical composition for treating triple-negative breast cancer. The pharmaceutical composition can reduce the dosage of known chemotherapeutic drugs in triple-negative breast cancer patients, reduce drug side effects, and improve prognosis. It can also delay the onset of disease caused by the accumulation of chemotherapeutic drugs in the body and extend the period during which patients can use chemotherapeutic drugs. It can also inhibit the proliferation of triple-negative breast cancer and effectively inhibit the metastasis of triple-negative breast cancer cells to other organs. That is, the pharmaceutical composition provided by the present invention can be used to treat metastatic triple-negative breast cancer or advanced triple-negative breast cancer. [Brief explanation of the drawings]

[0014] [Figure 1] FIG. 1 is a schematic diagram showing how the pharmaceutical composition for treating triple-negative breast cancer according to the present invention binds to the sequence d(AGCCGT)2 to form a complex (drug A is actinomycin, and drug D is doxorubicin). [Figure 2A] FIG. 1 shows the results of treating MDA-MB-231 cells with different ratios of actinomycin and doxorubicin (A represents actinomycin, and X represents doxorubicin). [Figure 2B] FIG. 1 shows the results of treating 4T1 cells with different ratios of actinomycin and doxorubicin (A represents actinomycin, and X represents doxorubicin). [Figure 2C] FIG. 1 shows the results of treating MCF-7 cells with different ratios of actinomycin and doxorubicin (A represents actinomycin, and X represents doxorubicin). [Figure 3] FIG. 1 shows the results of CI index calculation and analysis of cytotoxicity when different cancer cells are treated with different ratios of actinomycin and doxorubicin. [Figure 4A]FIG. 1 shows the calculation of the global synergy score obtained by treating MDA-MB-231 cells with different ratios of actinomycin and doxorubicin (A stands for actinomycin, DOX stands for doxorubicin). [Figure 4B] FIG. 1 shows the calculation of the global synergy score obtained by treating 4T1 cells with different ratios of actinomycin and doxorubicin (A stands for actinomycin, DOX stands for doxorubicin). [Figure 4C] FIG. 1 shows the calculation of the global synergy score obtained by treating MCF-7 cells with different ratios of actinomycin and doxorubicin (A stands for actinomycin, DOX stands for doxorubicin). [Figure 5] FIG. 1 shows the cell cycle distribution obtained after treatment of MDA-MB-231 and 4T1 cells with different therapeutic regimens. [Figure 6A] FIG. 1 shows the results of statistical analysis of cell cycle distribution obtained after treatment of MDA-MB-231 cells with different therapeutic regimens. [Figure 6B] FIG. 1 shows the results of a statistical analysis of cell cycle distribution obtained after treatment of M4T1 cells with different therapeutic regimens. [Figure 7] Heat maps of transcriptome changes obtained after treating MDA-MB-231 cells with different therapeutic regimens. [Figure 8A] FIG. 1 shows a protein-protein interaction network diagram of the combination therapy compared to the control group. [Figure 8B] FIG. 1 is a protein-protein interaction network diagram of the combination therapy compared to the doxorubicin treatment group. [Figure 9] FIG. 1 shows the results of a thermal stability test performed using the sequence of SEQ ID NO: 1 in combination with different drugs. [Figure 10] FIG. 1 shows an analysis of melting point changes in each treatment group. [Figure 11]FIG. 1 shows CD spectra obtained after reacting actinomycin, doxorubicin, and actinomycin and doxorubicin with different sequences (A represents actinomycin, and X represents doxorubicin). [Figure 12] FIG. 1 shows changes in tumor volume in mice of each group. [Figure 13] FIG. 1 shows changes in white blood cell counts in mice of each group. [Figure 14] FIG. 1 shows changes in body weight of mice in each group. [Figure 15] FIG. 1 shows the results of an analysis of tumor weight in mice of each group. [Figure 16] FIG. 1 shows the results of an analysis of liver weight relative to body weight for mice in each group. [Figure 17] FIG. 1 shows the results of an analysis of heart weight relative to body weight for each group of mice. [Figure 18] FIG. 1 shows the number of tumors metastasized to the lungs of mice in each group. [Figure 19] FIG. 1 shows the number of tumors metastasized to the liver of mice in each group. [Figure 20] FIG. 1 shows the results of H&E staining of lung and liver tissue sections from mice subjected to different treatments. DETAILED DESCRIPTION OF THE INVENTION

[0015] The present invention provides a pharmaceutical composition for treating triple-negative breast cancer, comprising actinomycin and doxorubicin. By administering an effective amount of the pharmaceutical composition for treating triple-negative breast cancer of the present invention to a breast cancer patient, actinomycin and doxorubicin intercalate into the nucleic acid sequence GCCG, and the pharmaceutical composition can target and bind to the nucleic acid sequence containing GCCG, thereby treating or inhibiting the growth and metastasis of triple-negative breast cancer and reducing the side effects of the drugs.

[0016] When actinomycin and doxorubicin are combined in a certain ratio range, a synergistic effect is created between the two drugs, with actinomycin cooperatively promoting the intercalation of doxorubicin into the GCCG site in the nucleic acid sequence and forming a complex with the nucleic acid sequence. Actinomycin allows doxorubicin to target and bind to the GCCG nucleic acid sequence, thereby reducing the possibility of doxorubicin binding to non-target sequences, effectively reducing the dosage of doxorubicin, extending the medication period for patients and reducing the incidence of side effects.

[0017] In the case of breast cancer cells, particularly triple-negative breast cancer cells, the pharmaceutical composition of the present invention can inhibit the proliferation of breast cancer cells when the dose ratio or concentration ratio of actinomycin to doxorubicin is 1:100 to 1:600, for example, 1:100, 1:200, 1:300, 1:400, 1:500, or 1:600. Specifically, when the actinomycin dose is 20 μg / kg, the doxorubicin dose can be 2,000 to 12,000 μg / kg, and when the actinomycin concentration is 2 nM, the doxorubicin concentration can be 200 nM to 1,200 nM.

[0018] In one embodiment of the present invention, when the subject of administration is a human, the effective amount of actinomycin D and doxorubicin in the pharmaceutical composition is preferably a ratio of 1:10 to 1:30, for example, 1:15, 1:20, or 1:22, and more preferably a ratio of 1:25 between actinomycin D and doxorubicin.

[0019] As shown in Figure 1, the pharmaceutical composition for treating triple-negative breast cancer according to the present invention disrupts the proliferation and metastasis of cancer cells through a complex formed by the binding of actinomycin and doxorubicin to the sequence d(AGCCGT)2, thereby achieving the effect of treating or ameliorating triple-negative breast cancer.

[0020] The pharmaceutical composition for treating triple-negative breast cancer of the present invention utilizes the synergistic effect of actinomycin and doxorubicin to suppress genes related to the RAS pathway, thereby suppressing triple-negative breast cancer at a dose that is more than half that of actinomycin and doxorubicin, thereby reducing the side effects of the drugs.

[0021] Since actinomycin and doxorubicin can target and intercalate GCCG sequences in nucleic acid molecules, another embodiment of the present invention discloses a nucleic acid intercalator that has actinomycin D and doxorubicin as active ingredients and binds to GCCG sequences contained in nucleic acid molecules.

[0022] The term "triple-negative breast cancer (TNBC)" refers to a subtype of breast cancer that does not express estrogen receptors (ER), progesterone receptors (PR), or human epidermal growth factor receptor type 2 (HER2), and accounts for approximately 15% of all breast cancers. In the present invention, "triple-negative breast cancer" also includes metastatic triple-negative breast cancer.

[0023] The term "pharmaceutical composition" means a composition containing at least two active ingredients that can be used to provide a therapeutic effect for a disease or related condition, and which have a synergistic effect between the active ingredients.

[0024] The term "treatment" means ameliorating, alleviating, or suppressing the progression of the disease or condition to which the term applies, or one or more symptoms of the disease or condition, or preventing the disease or complication to which the term applies.

[0025] The term "effective amount" means the amount of a compound or pharmacologically acceptable salt administered to relieve one or more symptoms of the disease being treated, reduce the discomfort associated with one or more symptoms, or ameliorate the course of the disease.

[0026] Actinomycin D (ActD), also known as actinomycin, is a type of actinomycin polypeptide antibiotic isolated from soil-borne Streptomyces bacteria and can be used as a chemotherapy drug. Actinomycin is used to inhibit RNA synthesis and protein synthesis, and is primarily used to treat nephroblastoma, testicular tumors, and rhabdomyomas.

[0027] The term "doxorubicin (abbreviated as Dox)" refers to a compound having the chemical formula (I) below, a molar mass of 543.52 g / mol, and a molecular formula of C 27 H 29 NO 11 Doxorubicin is a drug used to treat various cancers. It belongs to the anthracycline antibiotic family and its primary mechanism of action is to inhibit DNA and RNA synthesis by binding to DNA in the cell nucleus, as well as to inhibit the growth and division of cancer cells. Doxorubicin is typically part of chemotherapy regimens in the clinical treatment of breast cancer. For example, in the treatment of invasive breast cancer, doxorubicin is used in combination with cyclophosphamide. However, when doxorubicin is used in combination with other chemotherapy drugs, various side effects can occur, including bone marrow suppression (hematopoietic dysfunction), nausea, vomiting, hair loss, cardiotoxicity (myocardial damage), and hepatotoxicity. Furthermore, a serious side effect of doxorubicin is dilated cardiomyopathy, and the incidence of cardiomyopathy is positively correlated with the cumulative dose of doxorubicin. Currently, there is no established effective treatment for cardiomyopathy in clinical practice, so doxorubicin cannot be used as a long-term treatment option for patients with triple-negative breast cancer.

[0028] [ka]

[0029] The cells used in the following examples, such as the MDA-MB-231 (human triple-negative breast cancer) cell line, the 4T1 (mouse triple-negative breast cancer) cell line, and the MCF-7 (breast cancer) cell line, are readily available to those skilled in the art and do not require deposition. The 4T1 cell line is widely used as a research model for distant metastasis of breast cancer and as a breast cancer model for clinical drug screening.

[0030] The sequences d(AGCCCT)2, d(AGCACGT)2, etc. used in the following examples are artificially synthesized sequences, and are intended to verify that the pharmaceutical composition of the present invention has the property of targeting the GCCG sequence, but are not intended to limit the efficacy of the present invention.

[0031] Dosages used in the cell or animal studies in the following examples are for illustrative purposes only and are not intended to limit the scope of the invention.

[0032] Example 1: Synergistic Cytotoxicity Test Table 1 below shows the half maximal inhibitory concentrations (IC50) of various chemotherapeutic agents, such as actinomycin, doxorubicin, cisplatin, and 5FU, against MDA-MB-231 cells, 4T1 cells, and MCF-7 cells.

[0033] [Table 1]

[0034] MDA-MB-231, 4T1, and MCF-7 cells were treated with different ratios of actinomycin and doxorubicin for 48 hours, and the combination index (CI index) was calculated based on the cytotoxicity. The results are shown in Figures 2, 3, and Table 2. A CI index of less than 0.9 indicates a synergistic effect of the drug combination. A CI index of 0.9-1.0 indicates an additive effect of the drugs. Figure 3 shows that the CI index for the cytotoxicity of actinomycin and doxorubicin at different ratios against various breast cancer-related cell lines was all less than 0.9, indicating a synergistic effect between actinomycin and doxorubicin.

[0035] [Table 2]

[0036] The combined reaction data of actinomycin and doxorubicin was calculated using SynergyFinder, and interactive analysis and visualization were performed. The results are shown in Figure 4. The results in Figure 4 show that the overall synergy score is greater than 10, indicating that the interaction between actinomycin and doxorubicin is synergistic in each breast cancer cell line.

[0037] Example 2: Cell Test (1) MDA-MB-231 and 4T1 cells were treated with actinomycin (0.25 nM), doxorubicin (5 nM), or a combination of actinomycin (0.25 nM) and doxorubicin (5 nM) for 24 hours, nucleic acids were labeled with propidium iodide, and cell cycle analysis was performed by flow cytometry. The results are shown in Figures 5 and 6.

[0038] The results in Figures 5 and 6 show that actinomycin can enhance the cell cycle arrest at the G2 / M phase of triple-negative breast cancer cells induced by doxorubicin, i.e., the pharmaceutical composition for treating triple-negative breast cancer according to the present invention can effectively suppress the proliferation of triple-negative breast cancer and exert a therapeutic effect on triple-negative breast cancer.

[0039] Example 3: Cell Test (II) MDA-MB-231 cells were treated with actinomycin (2 nM), doxorubicin (600 nM), or a combination of actinomycin (2 nM) and doxorubicin (600 nM) for 24 hours, and the transcriptome changes of each cell group were recorded. The results are shown in Figure 7. Furthermore, software analysis yielded protein-protein interaction networks for each cell group, as shown in Figure 8.

[0040] Example 4: GCCG sequence-specific binding test The sequence shown in SEQ ID NO: 1 (concentration 2 μM) was reacted with actinomycin, doxorubicin, and actinomycin and doxorubicin, respectively. The dosage ratio of the sequence to the drug in each single-agent treatment group was 1:1, but the dosage ratio of the sequence to actinomycin and doxorubicin in the pharmaceutical composition of the present invention was 1:1:1. The binding state between the drug and each sequence and the change in melting point temperature in each of the above treatment groups were analyzed, and the results are shown in Figures 9 and 10. The results in Figures 9 and 10 indicate that actinomycin and doxorubicin can form complexes with the sequence shown in SEQ ID NO: 1.

[0041] Furthermore, the artificial synthetic sequences shown in Table 4 were reacted with different doses or ratios of actinomycin, doxorubicin, and actinomycin and doxorubicin, and the CD spectra of each treatment group were analyzed, with the results shown in Figure 11. The results in Figure 11 demonstrate that actinomycin can bind to the GCCG nucleic acid sequence in cooperation with doxorubicin. In other words, the pharmaceutical composition for treating triple-negative breast cancer according to the present invention can target and bind to the GCCG nucleic acid sequence, making it possible to maintain the effect of inhibiting or treating triple-negative breast cancer while reducing the dose of doxorubicin.

[0042] [Table 3]

[0043] Example 5: Animal Experiments Based on the common knowledge in the art, an MDA-MB-231 breast cancer mouse model was established, and the piglets in each group were given the following treatments on days 0, 7, 14, 21, 28, 35, 42, and 49 of the experiment: Group 1: no treatment; Group 2: Actinomycin was administered at a dose of 20 μg / kg (corresponding to the human clinical dose of 15 μg / kg), Group 3: Doxorubicin at a dose of 0.5 mg / kg (human clinical dose 20 mg / m 2 (equivalent to ) administered Group 4: Actinomycin (20 μg / kg) and doxorubicin (0.5 mg / kg) were administered in combination. Group 5: Actinomycin (10 μg / kg) and doxorubicin (0.25 mg / kg) were administered in combination at a dose 0.5 times that of Group 4.

[0044] During the experimental period, changes in tumor volume, white blood cell count, and body weight of the mice in each group were measured, and the results are shown in Figures 12 to 14. After the experiment was completed, the weights of the tumor, liver, and heart of the mice in each group were analyzed, and the results are shown in Figures 15 to 17.

[0045] 12 to 17, administration of the pharmaceutical composition for treating triple-negative breast cancer according to the present invention did not affect the body weight, liver weight, or heart weight of individuals with triple-negative breast cancer, demonstrating the safety of the pharmaceutical composition. Furthermore, the pharmaceutical composition for treating triple-negative breast cancer according to the present invention significantly reduced tumor volume and tumor weight at both the 1x dose and the 0.5x dose, demonstrating that the pharmaceutical composition of the present invention can achieve therapeutic effects even when the doses of actinomycin and doxorubicin are reduced due to the synergistic effect of actinomycin and doxorubicin.

[0046] From the above explanation, it can be seen that the pharmaceutical composition of the present invention can reduce the dosage of actinomycin and doxorubicin by at least half, and therefore the pharmaceutical composition of the present invention can effectively reduce the side effects of actinomycin and doxorubicin on individuals, extend the drug administration period in individuals, and achieve the effects of improving therapeutic effects and prognosis.

[0047] (Example 6: Cell metastasis inhibition experiment) A 4T1 breast cancer mouse model was established based on the general knowledge in the art. The experimental period was 5 weeks. Each group of piglets was treated under the following conditions on days 0, 7, 14, 21, 28, and 35 of the experiment: Group 1: no treatment; Group 2: Cyclophosphamide was administered at a dose of 5 mg / kg. Group 3: Cyclophosphamide (dose 5 mg / kg) and doxorubicin (dose 0.5 mg / kg) (human clinical dose 20 mg / m 2 (equivalent to) was administered concomitantly, Group 4: Actinomycin was administered at a dose of 20 μg / kg (corresponding to the human clinical dose of 15 μg / kg). Group 5: Doxorubicin was administered at a dose of 0.5 mg / kg; Group 6: Actinomycin (20 μg / kg) and doxorubicin (0.5 mg / kg) were administered in combination. Group 7: Actinomycin (10 μg / kg) and doxorubicin (0.25 mg / kg) were administered in combination at a dose 0.5 times that of Group 4.

[0048] After the experiment was completed, the piglets from each group were sacrificed and the number of tumors metastasized to the lungs and liver was examined. The results are shown in Figures 18 and 20. Tissue sections of the piglets' lungs and livers were also collected and stained with H&E, and the results are shown in Figure 20.

[0049] As can be seen from the results in Figures 18-20, the number of liver and lung tumors in Groups 2 and 3 mice was only slightly reduced compared to Group 1 mice, indicating that the therapeutic effect of cyclophosphamide alone or the combination of cyclophosphamide and doxorubicin on breast cancer metastasis was not significant. The number of lung and liver tumors in Group 4 mice was increased compared to Group 3 mice, indicating that the effect of actinomycin alone on breast cancer cell metastasis was not satisfactory. The number of lung tumors in Group 5 mice was almost the same as that in Group 3 mice, but the number of liver tumors was significantly lower than that in Group 1 mice, indicating that doxorubicin alone is effective against metastasis to only some organs but does not effectively suppress breast cancer metastasis overall. The number of liver and lung tumors in Group 6 mice was significantly reduced, indicating that the combination of the pharmaceutical composition of the present invention effectively treats metastatic breast cancer. The mice in Group 7 were also administered the composition of the present invention, but the dose was half that of the mice in Group 6, so the effect of inhibiting metastasis of breast cancer cells to the liver and lungs was worse than that of the mice in Group 6.

[0050] The results of this example prove that the pharmaceutical composition of the present invention not only inhibits the proliferation of triple-negative breast cancer, but also effectively inhibits the metastasis of triple-negative breast cancer cells to other organs, indicating that the pharmaceutical composition of the present invention can be used to treat metastatic triple-negative breast cancer or advanced triple-negative breast cancer.

Claims

1. 1. Use of a chemotherapeutic agent in the preparation of a pharmaceutical composition for treating triple-negative breast cancer and metastasis thereof, comprising: The use, characterized in that the chemotherapeutic agent comprises Actinomycin D and Doxorubicin.

2. 2. The use according to claim 1, characterized in that the pharmaceutical composition consists of actinomycin D and doxorubicin.

3. The use according to claim 1 or 2, wherein the dosage ratio of actinomycin D to doxorubicin is 1:10 to 1:30 when the subject of administration of the pharmaceutical composition is a human.

4. The use according to claim 3, wherein the dosage ratio of actinomycin D to doxorubicin is 1:25 when the subject of administration of the pharmaceutical composition is a human.

5. 3. The use according to claim 1 or 2, characterized in that the pharmaceutical composition is used for targeting and binding the nucleic acid sequence GCCG.

6. Use of a chemotherapeutic agent in the preparation of a nucleic acid intercalator, comprising: The use, characterized in that the chemotherapy drugs include actinomycin D and doxorubicin, and the nucleic acid intercalator is used to bind to the GCCG sequence in the nucleic acid molecule.

7. The use according to claim 6, characterized in that the nucleic acid intercalator consists of actinomycin D and doxorubicin.

8. The use according to claim 6 or 7, characterized in that when the subject to which the nucleic acid intercalator is administered is a human, the dosage ratio of actinomycin D to doxorubicin is 1:10 to 1:

30.

9. 9. The use according to claim 8, characterized in that the dosage ratio of actinomycin D to doxorubicin is 1:25.

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