Application of dehydroandrographolide in preparation for preventing and / or treating breast cancer and pharmaceutical composition of dehydroandrographolide

Abstract

The invention relates to application of dehydroandrographolide in a medicament for preventing and / or treating breast cancer and a pharmaceutical composition of the dehydroandrographolide. According to the application disclosed by the invention, the dehydroandrographolide has the effects of obviously inhibiting the expression of an epidermal growth factor receptor (EGFR) and phosphatidylinositol 3-kinase (PIK3R1) and inhibiting cell migration; the compound has the effects of inhibiting expression of mitogen-activated protein kinase 3 (MAPK3), down-regulating expression of B cell lymphoma / leukemia 2 gene (Bcl-2), increasing expression of Bcl-2 related X protein (Bax) and promoting cell apoptosis, and can be used for preventing or treating breast cancer. The invention aims to provide application of dehydroandrographolide in preventing and treating breast cancer, and further relates to a medication scheme for preventing and treating breast cancer.

Description

Technical Field

[0001] The present invention relates to the field of pharmacology and toxicology, and in particular to the use of dehydroandrographolide (DEH) in a medicament for preventing and / or treating breast cancer and a pharmaceutical composition thereof. Background Art

[0002] Breast cancer is one of the most common cancers in women, characterized by high morbidity and mortality. A variety of treatments for breast cancer have been developed, including surgery, radiotherapy, chemotherapy, and endocrine therapy. However, these methods have significant side effects and drug resistance, and the treatment effect is poor. Traditional Chinese medicine is widely accepted as a complementary and alternative therapy for cancer because of its large sources, low toxicity, and multi-target and multi-pathway mechanism of action. Dehydroandrographolide is one of the main components of Andrographis paniculata, which has antiviral, anti-inflammatory, and hypoglycemic effects. However, its efficacy in the treatment of breast cancer has not been explored. Summary of the invention

[0003] The purpose of the present invention is to provide the use of dehydroandrographolide in a medicament for preventing and / or treating breast cancer and a pharmaceutical composition thereof, so as to provide a new therapeutic drug for breast cancer.

[0004] The present invention is achieved through the following technical solutions:

[0005] In one aspect, the present invention provides use of dehydroandrographolide in a medicament for preventing and / or treating breast cancer.

[0006] Furthermore, in the use of the dehydroandrographolide in a medicament for preventing and / or treating breast cancer, the dehydroandrographolide inhibits the proliferation and migration of human breast cancer cells MDA-MB-231.

[0007] Furthermore, in the use of the dehydroandrographolide in a medicament for preventing and / or treating breast cancer, the dehydroandrographolide reduces the expression of epidermal growth factor receptor (EGFR) and phosphatidylinositol 3-kinase (PIK3R1), and inhibits cell migration.

[0008] Furthermore, in the use of the dehydroandrographolide in a medicament for preventing and / or treating breast cancer, the dehydroandrographolide inhibits the expression of mitogen-activated protein kinase 3 (MAPK3), downregulates the expression of B-cell lymphoma / leukemia-2 gene (Bcl-2), increases the expression of Bcl-2 associated X protein (Bax), and promotes apoptosis of tumor cells.

[0009] Another aspect of the present invention provides a pharmaceutical composition for preventing and / or treating breast cancer, the pharmaceutical composition comprising a mixture of a dehydroandrographolide compound in a therapeutically effective amount and at least one pharmaceutically acceptable excipient.

[0010] Furthermore, in the pharmaceutical composition for preventing and / or treating breast cancer, the pharmaceutical composition is added with excipients acceptable in the field of preparations to be made into tablets, capsules, granules, powders, oral solutions or injections.

[0011] Furthermore, in the pharmaceutical composition for preventing and / or treating breast cancer, the pharmaceutically acceptable excipients added include at least one of fillers, disintegrants, lubricants, suspending agents, binders, sweeteners, flavoring agents, and preservatives.

[0012] Furthermore, in the pharmaceutical composition for preventing and / or treating breast cancer, the filler is selected from at least one of starch, pregelatinized starch, lactose, mannitol, chitosan, microcrystalline cellulose, and sucrose;

[0013] And / or, the disintegrant is selected from at least one of starch, pregelatinized starch, microcrystalline cellulose, sodium carboxymethyl starch, cross-linked polyvinyl pyrrolidone, low-substituted hydroxypropyl cellulose, and cross-linked sodium carboxymethyl cellulose.

[0014] Furthermore, in the pharmaceutical composition for preventing and / or treating breast cancer, the lubricant is selected from at least one of magnesium stearate, sodium lauryl sulfate, talc and silicon dioxide.

[0015] Furthermore, in the pharmaceutical composition for preventing and / or treating breast cancer, the suspending agent is selected from at least one of polyvinyl pyrrolidone, microcrystalline cellulose, sucrose, agar, and hydroxypropyl methylcellulose;

[0016] And / or, the adhesive is selected from at least one of starch slurry, polyvinyl pyrrolidone and hydroxypropyl methylcellulose.

[0017] Further, in the pharmaceutical composition for preventing and / or treating breast cancer, the flavoring agent is selected from: sweeteners and flavors;

[0018] And / or, the sweetener is selected from at least one of saccharin sodium, aspartame, sucrose, cyclamate, and glycyrrhetinic acid.

[0019] As used herein, "pharmaceutically acceptable" means that the compound or composition must be chemically and / or toxicologically compatible with the other ingredients contained in the formulation.

[0020] The "therapeutically effective amount" refers to the amount of the compound of the present invention that treats or prevents a specific disease or symptom; reduces, improves or eliminates one or more symptoms of a specific disease; or prevents or delays the onset of a specific disease or symptom. The specific therapeutic dose depends on the severity of the disease and the duration of treatment. The doctor determines the appropriate dose based on the disease and the specific conditions of the patient being treated.

[0021] Compared with the prior art, the present invention has the following advantages and beneficial effects:

[0022] The dehydroandrographolide disclosed by the invention has the effects of significantly inhibiting the expression of epidermal growth factor receptor (EGFR) and phosphatidylinositol 3-kinase (PIK3R1), inhibiting cell migration, inhibiting the expression of mitogen-activated protein kinase 3 (MAPK3), down-regulating the expression of B cell lymphoma / leukemia-2 gene (Bcl-2), increasing the expression of Bcl-2 associated X protein (Bax), promoting the apoptosis of tumor cells, and can be used for preventing or treating breast cancer.

[0023] The dehydroandrographolide of the present invention has been confirmed by cell experiments to inhibit the proliferation and migration of MDA-MB-231 cells in a concentration- and time-dependent manner, and significantly promote cell apoptosis, indicating that it has an anti-breast cancer effect. Animal experiments have shown that dehydroandrographolide can inhibit tumor growth, indicating that dehydroandrographolide has certain preventive and therapeutic effects.

[0024] Based on nuclear magnetic resonance metabolomics combined with multivariate statistical methods, the metabolic pathways involved in the regulation of dehydroandrographolide in the treatment of breast cancer were studied, including aminoacyl-tRNA biosynthesis, TCA cycle, phenylalanine metabolism, glycolysis / gluconeogenesis, alanine, aspartate and glutamate metabolism, glyoxylate and dicarboxylic acid metabolism, arginine biosynthesis, etc.

[0025] Through the joint analysis of network pharmacology prediction targets and metabolic pathway-related targets, the core targets of drug treatment for breast cancer were found, molecular docking was used to study the binding effect of drugs and targets, and the effect of drugs on the expression of core targets was verified by real-time fluorescence quantitative PCR (qPCR). The results showed that the core targets of dehydroandrographolide against breast cancer were EGFR, MAPK3, PIK3R1, etc. Dehydroandrographolide can significantly reduce the expression of EGFR and PIK3R1, inhibit cell migration, inhibit the expression of mitogen-activated protein kinase 3 (MAPK3), downregulate the expression of B cell lymphoma / leukemia-2 gene (Bcl-2), increase the expression of Bcl-2-associated X protein (Bax), and promote tumor cell apoptosis.

[0026] The dehydroandrographolide disclosed by the invention has the effects of significantly inhibiting the expression of epidermal growth factor receptor (EGFR) and phosphatidylinositol 3-kinase (PIK3R1), inhibiting cell migration, inhibiting the expression of mitogen-activated protein kinase 3 (MAPK3), down-regulating the expression of B cell lymphoma / leukemia-2 gene (Bcl-2), increasing the expression of Bcl-2 associated X protein (Bax), promoting the apoptosis of tumor cells, and can be used for preventing or treating breast cancer. BRIEF DESCRIPTION OF THE DRAWINGS

[0027] In order to more clearly illustrate the technical solutions of the exemplary embodiments of the present invention, the following briefly introduces the drawings required for use in the embodiments. It should be understood that the following drawings only illustrate certain embodiments of the present invention and should not be regarded as limiting the scope. For ordinary technicians in this field, other relevant drawings can be obtained based on these drawings without creative work.

[0028] In the figure:

[0029] Figure 1 is the cell growth curve of drug action;

[0030] Figure 2 This is a diagram showing the effect of drugs on cell apoptosis;

[0031] Figure 3 It is a statistical diagram of drug effects on cell apoptosis;

[0032] Figure 4 for the effects of drugs on the cell cycle;

[0033] Figure 5 It is a statistical diagram of the effect of drugs on the cell cycle;

[0034] Figure 6 This is an experimental diagram of the effect of drugs on cell scratch healing;

[0035] Figure 7 This is a statistical graph of drug effects on cell migration experiments;

[0036] Figure 8 The effect of the drug on the mRNA expression of the core target;

[0037] Fig. 9 This is a picture of the tumor tissue morphology results of drug action;

[0038] Fig.10 This is a graph showing the weight of tumor tissue under drug effects. DETAILED DESCRIPTION

[0039] In order to make the purpose, technical scheme and advantages of the present invention clearer, the present invention is further described in detail below in conjunction with examples and drawings. The illustrative embodiments of the present invention and their description are only used to explain the present invention and are not intended to limit the present invention. If specific conditions are not specified in the examples, they are carried out according to conventional conditions or conditions recommended by the manufacturer. If the manufacturer is not specified for the reagents or instruments used, they are all conventional products that can be purchased commercially.

[0040] The chemical formula of dehydroandrographolide is as follows:

[0041]

[0042] The effect of dehydroandrographolide on breast cancer was confirmed by the following methods in human breast cancer MDA-MB-231 cells and animal experiments. The following is a specific experiment.

[0043] 1. Materials and Methods

[0044] 1. Reagents

[0045] Gibco fetal bovine serum (Thermo Fisher Scientific, USA), TRIzol reagent (Shenzhen Kangrun Biotechnology Co., Ltd.), diethyl pyrocarbonate (DEPC) treated water, BeyoRT TM III cDNA Synthesis Kit, BeyoFast TM SYBR Green qPCR Mix reagent and Methyl thiazolyltetrazolium (MTT) were purchased from Shanghai Biotech Biotechnology Co., Ltd.; PCR primers were purchased from Beijing Qingke Biotechnology Co., Ltd.; AnnexinV-FITC / PI apoptosis detection kit and cell cycle detection kit were purchased from Jiangsu Keyi Biotechnology Co., Ltd.; 3-(Trimethylsilyl)propionic acid-d4 sodium salt (TSP, Sigma-Aldrich, USA); and heavy water was purchased from Beijing Myrida Technology Co., Ltd.

[0046] 2. Experimental Equipment

[0047] NanoDrop micro-volume spectrophotometer (Thermo Fisher Scientific, USA), Light Cycler 96 real-time fluorescence quantitative PCR instrument (Roche, Switzerland), BX-53 inverted fluorescence microscope (Olympus, Japan), NovoCyte 2060R flow cytometer (Essen Biosciences, USA), BB15 cell culture incubator (Thermo Fisher Scientific, USA), Avance II 600 MHz nuclear magnetic resonance spectrometer (Bruker, Switzerland).

[0048] 3. Cell Culture

[0049] Human breast cancer MDA-MB-231 cells were cultured in a constant temperature incubator at 37°C and 5% CO2. The complete culture medium was prepared with DMEM culture medium, 10% fetal bovine serum and 1% double antibody solution. The culture medium was changed every two days and the cells were passaged twice a week at a ratio of 1:4.

[0050] 4. Animals

[0051] Eighteen SPF female Balb / c mice, 5 weeks old and weighing 15-18 g, were purchased from Beijing Huafukang Biotechnology Co., Ltd. with the license number SCXK (Beijing) 2019-0008.

[0052] 5. Drug administration

[0053] 5.1 Cellular administration

[0054] The drug was dissolved in ethanol to prepare a 10mM drug stock solution. The stock solution was then diluted with ethanol to obtain a series of drug standard solutions. After sterile filtration, 25μL of the drug standard solution was taken out and diluted to 1mL with serum-free medium to obtain the experimental drug solution. Adherent cells were given different concentrations of dehydroandrographolide solution: 0, 10, 20, 50, 100, 200, 500μM for 24 h or 48h, and a blank group was set up, and 6 replicates were set up for each group.

[0055] 5.2 Animal Dosing

[0056] After one week of adaptive feeding, 0.5 mL (4×106 cells / mouse) of breast cancer MDA-MB-231 cell suspension was injected into the third pair of mammary fat pads of mice. When the tumor grew to 50-100 mm3, the mice with successful modeling were randomly divided into three groups, namely the control group (Control), the 5-fluorouracil (5-Fu, 20 mg·kg-1) group, and the dehydroandrographolide (DEH, 20 mg·kg-1) group, with 6 mice in each group. The drugs were administered by intraperitoneal injection once a day for a total of 10 days.

[0057] 6. Test indicators and results

[0058] The following experimental results of cell apoptosis and proliferation were analyzed using GraphPad Prism 8.0 software, and the significance of differences between groups was evaluated by one-way ANOVA.

[0059] Metabolomics was analyzed using orthogonal partial least squares analysis with permutation test (OPLS-DA).

[0060] *P<0.05, compared with the control group, there is a statistical difference; **P<0.01, compared with the control group, the difference is relatively significant; ***P<0.001, compared with the control group, the difference is significant; ****P<0.0001, compared with the control group, the difference is extremely significant.

[0061] 6.1. MTT assay for cell proliferation

[0062] The cell growth curves of MDA-MB-231 cells after 24h and 48h of treatment with dehydroandrographolide are shown in Figure 2. Figure 1 shown.

[0063] from Figure 1 It can be seen that with the increase of drug concentration and action time, the survival rate of cells gradually decreased. This shows that the drug can inhibit the proliferation of MDA-MB-231 cells in a dose- and time-dependent manner. After acting on MDA-MB-231 cells for 24h and 48h, the IC50 was 154.6μM (51.39μg / mL) and 96.98μM (32.24μg / mL), respectively.

[0064] 6.2. Annexin V-FITC / PI double staining to detect cell apoptosis

[0065] Annexin V-FITC / PI double staining flow cytometry was used to analyze cell apoptosis. Figure 2 , Figure 3 As shown. Flowjo software can be used to process the flow cytometry graph to obtain the cell apoptosis rate. The Q1 quadrant represents necrotic cells, the Q2 quadrant represents late apoptotic cells, the Q3 quadrant represents early apoptotic cells, and the Q4 quadrant represents normal cells.

[0066] from Figure 2 and Figure 3 It can be seen that when the cells were incubated with dehydroandrographolide for 24 hours and the drug concentration was 20μg / mL and 50μg / mL, the total cell apoptosis rate was 7.87%±0.32% and 11.73%±0.94%, respectively, which was significantly higher than that of the control group (P<0.001, P<0.0001). Therefore, dehydroandrographolide can induce cell apoptosis, and early apoptosis is the main cause.

[0067] 6.3. PI single staining to detect cell cycle

[0068] PI staining flow cytometry was used to observe the ratio of cells in various division stages after drug treatment. Figure 4 , Figure 5 As shown, the flow cytometer has three peaks. The left peak represents cells in the G0 / G1 phase, the right peak represents cells in the G2 / M phase, and the middle peak represents cells in the S phase.

[0069] from Figure 4 and Figure 5 It can be seen that after 24 hours of dehydroandrographolide treatment, the proportion of G0 / G1 phase cells increased compared with the control group (P<0.0001), and as the drug concentration increased, the proportion also increased; S phase and G2 / M phase cells were significantly reduced compared with the control group under the action of 50μg / mL AND (P<0.01, P<0.05). The results showed that dehydroandrographolide mainly blocked MDA-MB-231 cells in the G0 / G1 phase, and there was a dose-dependent effect.

[0070] 6.4. Scratch test to determine the effect of drugs on cell healing ability

[0071] The effect of drugs on the invasion ability of MDA-MB-231 cells was investigated by scratching. Figure 6 , Figure 7 shown.

[0072] from Figure 6 and Figure 7 It can be seen that under the action of different concentrations of dehydroandrographolide, the scratch healing ability of the drug-treated group was weakened, which was significantly different from that of the control group (20, 50 μg / mL, P<0.01, P<0.0001, respectively), showing time and dose dependence.

[0073] 6.5. Mechanism of action of dehydroandrographolide in the treatment of breast cancer

[0074] The network pharmacology method was used to collect drug and breast cancer targets based on network database retrieval, and the protein-protein interaction (PPI) network was constructed using the STRING database to screen out key genes. The targets were enriched in the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways using Rstudio. The results are shown in Table 1.

[0075] Table 1 Network pharmacology analysis of breast cancer pathways involved in the targets of dehydroandrographolide

[0076]

[0077]

[0078] As can be seen from Table 1, the pathways involved in the targets of dehydroandrographolide are: endocrine resistance, EGFR tyrosine kinase inhibitor resistance, prostate cancer, proteoglycans in cancer, pancreatic cancer, chemical carcinogen-receptor activation, PI3K-AKT signaling pathway, progesterone-mediated oocyte maturation, ErbB signaling pathway, non-small cell lung cancer, breast cancer, etc., a total of 159. Among them, the cancer-related pathways are: proteoglycans in cancer (hsa05205), PI3K-AKT signaling pathway (hsa04151), ErbB signaling pathway (hsa04012), breast cancer (hsa05224), apoptosis (hsa04210), prolactin signaling pathway (hsa04917), microRNA and cancer (hsa05206), HIF-1 signaling pathway (hsa04066), etc., indicating that the anti-breast cancer effect of dehydroandrographolide is a multi-target and multi-pathway molecular mechanism.

[0079] Nuclear magnetic resonance (NMR) metabolomics technology combined with multivariate statistical analysis was used to study the mechanism of action of dehydroandrographolide in the treatment of breast cancer, to explore its regulated metabolites and related metabolic pathways, and to use the MetaboAnalyst 5.0 database to elucidate the metabolic pathways related to the anticancer effect of the drug. The results are shown in Table 2.

[0080] Table 2 Pathway enrichment analysis of differential metabolites in cells from the dehydroandrographolide administration group and the control group by NMR metabolomics analysis

[0081]

[0082]

[0083] Table 2 lists the basic information such as pathway name, t-test P value, false discovery rate (FDR), pathway impact value, etc. The main enriched pathways of metabolites regulated by the anticancer effect of dehydroandrographolide are: biosynthesis of aminoacyl-tRNA, TCA cycle, phenylalanine metabolism, glycolysis / gluconeogenesis, alanine, aspartate and glutamate metabolism, glyoxylate and dicarboxylic acid metabolism, arginine biosynthesis, etc.

[0084] The related targets of differential metabolites after drug administration in breast cancer cells were combined with the drug anti-breast cancer related targets in network pharmacology to construct a PPI network. The core targets of dehydroandrographolide in the treatment of breast cancer were analyzed using the "Network analysis" function of Cytoscape 3.8.2 software, and the core targets were screened according to the degree value. As shown in Table 3, the top 30 targets ranked by degree value are listed. The core targets of dehydroandrographolide in the treatment of breast cancer are AKT1, MAPK3, EGFR, MAPK1, PIK3R1, CASP3, PKM, MDH2, ESR1 and MDH1.

[0085] Table 3 Core targets of dehydroandrographolide against breast cancer (Top 30)

[0086]

[0087]

[0088] The qPCR method was used to verify the effects of these targets. The expression levels of each target detected were based on the glyceraldehyde-3-phosphate dehydrogenase gene (GAPDH). The results are shown in Figure 8 As shown in the data, the dehydroandrographolide administration group could reduce the mRNA expression of MAPK3 (P<0.01), the expression of EGFR and PIK3R1 was significantly decreased (P<0.001, P<0.001), the expression of AKT1 did not change significantly, but the expression of MAPK1 increased (P<0.05).

[0089] In addition, in order to study the apoptosis of cancer cells induced by dehydroandrographolide, the changes in the mRNA expression of apoptotic factors Bcl-2 and Bax after administration were also determined. Compared with the control group, the mRNA expression of Bax in the dehydroandrographolide administration group did not change significantly (P>0.05), the mRNA expression of Bcl-2 decreased significantly (P<0.001), and the expression ratio of Bax / Bcl-2 increased (P<0.01).

[0090] 6.6 Inhibitory effect of dehydroandrographolide on tumors in tumor-bearing mice

[0091] The experimental mice were given the drug for 10 days. On the last day, the mice were weighed and killed by cervical dislocation. The tumor tissue was completely removed. The morphology of the solid tumor was as follows: Fig. 9 As shown in Figure 2, the tumor volume in the dehydroandrographolide 20 mg kg-1 group was significantly reduced compared with the control group, but the effect was not as good as that in the 5-fluorouracil group. Fig.10 ) and calculate the tumor inhibition rate. The tumor inhibition rate calculation formula is as follows:

[0092] Tumor inhibition rate / %=(average tumor weight of control group-average tumor weight of drug-treated group) / average tumor weight of control group×100%.

[0093] The tumor weight of mice in the dehydroandrographolide 20 mg·kg-1 group was significantly reduced (P<0.05), and the tumor inhibition rate was 29.84%. As a positive drug, 5-fluorouracil had a tumor inhibition rate of 50.88%.

[0094] During the administration period, there was no significant difference in the body weight of mice in the DEH group compared with the Control group. On the 8th day, the 5-Fu group showed a significant difference compared with the Control group, and there were phenomena such as reduced food intake and diarrhea. The above results show that DEH has a certain tumor inhibitory effect and has less toxic side effects.

[0095] The specific implementation methods described above further illustrate the objectives, technical solutions and beneficial effects of the present invention in detail. It should be understood that the above description is only a specific implementation method of the present invention and is not intended to limit the scope of protection of the present invention. Any modifications, equivalent substitutions, improvements, etc. made within the spirit and principles of the present invention should be included in the scope of protection of the present invention.

Claims

1. Use of dehydroandrographolide in a medicament for preventing and / or treating breast cancer.

2. The use of dehydroandrographolide according to claim 1 in a medicament for preventing and / or treating breast cancer, characterized in that: The dehydroandrographolide inhibits the proliferation and migration of human breast cancer cells MDA-MB-231.

3. The use of dehydroandrographolide according to claim 1 in a medicament for preventing and / or treating breast cancer, characterized in that: The dehydroandrographolide reduces the expression levels of epidermal growth factor receptor EGFR and phosphatidylinositol 3-kinase PIK3R1, and inhibits cell migration.

4. The use of dehydroandrographolide in a medicament for preventing and / or treating breast cancer according to claim 1, characterized in that: The dehydroandrographolide inhibits the expression of mitogen-activated protein kinase 3 MAPK3, downregulates the expression of B-cell lymphoma / leukemia-2 gene Bcl-2, increases the expression of Bcl-2 related X protein Bax, and promotes tumor cell apoptosis.

5. A pharmaceutical composition for preventing and / or treating breast cancer, characterized in that: The pharmaceutical composition comprises a mixture of a dehydroandrographolide compound present in a therapeutically effective amount and at least one pharmaceutically acceptable excipient.

6. The pharmaceutical composition for preventing and / or treating breast cancer according to claim 5, characterized in that: The pharmaceutical composition can be added with acceptable auxiliary materials in the field of preparation to be made into tablets, capsules, granules, powders, oral solutions or injections.

7. The pharmaceutical composition for preventing and / or treating breast cancer according to claim 5, characterized in that: The added pharmaceutically acceptable excipients include at least one of fillers, disintegrants, lubricants, suspending agents, binders, sweeteners, flavoring agents, and preservatives.

8. The pharmaceutical composition for preventing and / or treating breast cancer according to claim 7, characterized in that: The filler is selected from at least one of starch, pregelatinized starch, lactose, mannitol, chitin, microcrystalline cellulose, and sucrose; And / or, the disintegrant is selected from at least one of starch, pregelatinized starch, microcrystalline cellulose, sodium carboxymethyl starch, cross-linked polyvinyl pyrrolidone, low-substituted hydroxypropyl cellulose, and cross-linked sodium carboxymethyl cellulose.

9. The pharmaceutical composition for preventing and / or treating breast cancer according to claim 2, characterized in that: The lubricant is selected from at least one of magnesium stearate, sodium lauryl sulfate, talc and silicon dioxide.

10. The pharmaceutical composition for preventing and / or treating breast cancer according to claim 2, characterized in that: The suspending agent is selected from at least one of polyvinyl pyrrolidone, microcrystalline cellulose, sucrose, agar, and hydroxypropyl methylcellulose; And / or, the adhesive is selected from at least one of starch slurry, polyvinyl pyrrolidone and hydroxypropyl methylcellulose.

11. The pharmaceutical composition for preventing and / or treating breast cancer according to claim 2, characterized in that: The flavoring agent is selected from: sweeteners and flavors; And / or, the sweetener is selected from at least one of saccharin sodium, aspartame, sucrose, cyclamate, and glycyrrhetinic acid.

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