A podophyllotoxin derivative and its application in preparing a drug for breast cancer and improving drug resistance of breast cancer

Abstract

The present invention relates to the field of biomedicine technology, and in particular to a podophyllotoxin derivative and its application in preparing a drug for breast cancer and improving breast cancer drug resistance. The present invention is directed to a new podophyllotoxin derivative methoxysulfonylamidinopodophyllotoxin (MSAPPT). After MSAPPT acts on human breast cancer cells and tamoxifen-resistant breast cancer cells, cell proliferation experiments and apoptosis experiments show that MSAPPT significantly inhibits the proliferation of breast cancer cells and tamoxifen-resistant breast cancer cells and significantly promotes the apoptosis of the two cells. Therefore, the podophyllotoxin derivative MSAPPT developed by the present invention can be used as a potential therapeutic drug for patients with breast cancer and tamoxifen-resistant breast cancer, and the drug has broad application prospects in the field of breast cancer treatment.

Description

Technical Field

[0001] The present invention relates to the technical field of biomedicine, and in particular to a podophyllotoxin derivative and its application in preparing a drug for breast cancer and improving the drug resistance of breast cancer. Background Art

[0002] Tamoxifen is the main endocrine therapy for ERα-positive breast cancer patients, and about 40% of patients will develop tamoxifen resistance. Recurrence and metastasis caused by tamoxifen resistance has become a difficult problem to be solved in the clinical treatment of ERα-positive breast cancer. It is very necessary to develop and design new chemotherapy drugs to prevent the occurrence of tamoxifen resistance and inhibit the progression of tamoxifen-resistant breast cancer.

[0003] Podophyllotoxin is the main alkaloid component in the rhizomes of Podophyllum plants. Studies have shown that it has good anti-tumor activity, but it cannot be used directly in clinical practice due to its severe toxicity. After structural modification of podophyllotoxin, the modified podophyllotoxin obtained has been widely used in the clinical treatment of leukemia, lung cancer, gastric cancer, ovarian cancer, etc., but there is no podophyllotoxin modified product that can be used to treat breast cancer. Summary of the invention

[0004] In order to overcome the shortcomings and deficiencies in the prior art, the object of the present invention is to provide a podophyllotoxin derivative and its use in preparing a drug for breast cancer and improving the drug resistance of breast cancer.

[0005] The purpose of the present invention is achieved by the following technical solution: a podophyllotoxin derivative, the structural formula of the podophyllotoxin derivative is as follows:

[0006]

[0007] Another object of the present invention is achieved through the following technical solution: use of the above-mentioned podophyllotoxin derivative in the preparation of a drug for breast cancer.

[0008] Preferably, the breast cancer is ERα-positive breast cancer.

[0009] Another object of the present invention is achieved by the following technical solution: use of the above-mentioned podophyllotoxin derivative in the preparation of a drug for improving the drug resistance of patients to breast cancer.

[0010] Preferably, the drug resistance is caused by the endocrine therapy drug tamoxifen.

[0011] Preferably, the breast cancer is ERα-positive breast cancer.

[0012] Another object of the present invention is achieved by the following technical solution: use of the above-mentioned podophyllotoxin derivative and tamoxifen in the preparation of a drug for breast cancer.

[0013] Preferably, the breast cancer is ERα-positive breast cancer.

[0014] The beneficial effect of the present invention is that: the present invention is directed to a new podophyllotoxin derivative methoxysulfonylamidinopodophyllotoxin (MSAPPT), and after MSAPPT acts on human breast cancer cells and tamoxifen-resistant breast cancer cells, cell proliferation experiments and apoptosis experiments show that MSAPPT significantly inhibits the proliferation of breast cancer cells and tamoxifen-resistant breast cancer cells and significantly promotes the apoptosis of the two cells. Therefore, the podophyllotoxin derivative MSAPPT developed by the present invention can be used as a potential therapeutic drug for patients with breast cancer and tamoxifen-resistant breast cancer, and the drug has broad application prospects in the field of breast cancer treatment. BRIEF DESCRIPTION OF THE DRAWINGS

[0015] Figure 1 This is the cell survival rate detection graph of MCF7 by MSAPPT;

[0016] Figure 2 This is a graph showing the cell viability of MCF7TR detected by MSAPPT;

[0017] Figure 3 This is a graph showing the apoptosis rate of MCF7 cells induced by MSAPPT (the right graph shows the cells with MSAPPT added, and the left graph shows the control group);

[0018] Figure 4 This is a graph showing the apoptosis rate of MCF7TR cells induced by MSAPPT (the right graph shows the cells with MSAPPT added, and the left graph shows the control group). DETAILED DESCRIPTION

[0019] In order to facilitate the understanding of those skilled in the art, the following embodiments and attached Figure 1-4 The present invention is further described, and the contents mentioned in the implementation modes are not intended to limit the present invention.

[0020] Example 1 Podophyllotoxin derivative MSAPPT

[0021] The chemical name of the podophyllotoxin derivative of the present invention is methoxysulfonyl amidine aminopodophyllotoxin (MSAPPT), and its structural formula is as follows:

[0022]

[0023] Example 2 Experimental study on the cell proliferation of MCF7 and MCF7TR by MSAPPT

[0024] Experimental steps:

[0025] 1. Breast cancer cells MCF7 and tamoxifen-resistant breast cancer cells MCF7TR were plated into 6-well plates 24 hours in advance;

[0026] 2. After adding different concentrations of P4E to the above two cells and culturing for 48 hours, the cell survival rate was detected by CCK-8 kit. The experimental results are as follows: Figure 1 and Figure 2 As shown, the results showed that MSAPPT significantly inhibited the proliferation of breast cancer cell line MCF7 and tamoxifen-resistant breast cancer cell line MCF7TR.

[0027] Example 2 Experimental study on apoptosis of MCF7 and MCF7TR cells by MSAPPT

[0028] Experimental steps:

[0029] 1. Breast cancer cells MCF7 and tamoxifen-resistant breast cancer cells MCF7TR were plated into 6-well plates 24 hours in advance;

[0030] 2. After culturing the two cells for 24 hours, 10ug / mL of MSAPPT was added. After 48 hours, the cell apoptosis rate was detected using the Annexin v / pi apoptosis detection kit. The experimental results are as follows: Figure 3 and Figure 4 As shown, the results showed that MSAPPT could significantly induce apoptosis in breast cancer cells MCF7 and tamoxifen-resistant breast cancer cells MCF7TR.

[0031] The present invention is directed to a new podophyllotoxin derivative methoxysulfonylamidinopodophyllotoxin (MSAPPT). After MSAPPT acts on human breast cancer cells and tamoxifen-resistant breast cancer cells, cell proliferation experiments and apoptosis experiments show that MSAPPT significantly inhibits the proliferation of breast cancer cells and tamoxifen-resistant breast cancer cells and significantly promotes the apoptosis of the two cells. Therefore, the podophyllotoxin derivative MSAPPT developed by the present invention can be used as a potential therapeutic drug for patients with breast cancer and tamoxifen-resistant breast cancer, and the drug has broad application prospects in the field of breast cancer treatment.

[0032] The above embodiments are preferred implementation schemes of the present invention. In addition, the present invention may also be implemented in other ways. Any obvious replacement without departing from the concept of the present invention is within the protection scope of the present invention.

Claims

1. Use of a podophyllotoxin derivative in the preparation of a drug for breast cancer, wherein the structural formula of the podophyllotoxin derivative is as follows:

2. Use of a podophyllotoxin derivative according to claim 1 in the preparation of a drug for breast cancer, Features: The breast cancer is ERα-positive breast cancer.

3. Use of a podophyllotoxin derivative in the preparation of a drug for improving a patient's resistance to breast cancer, wherein the structural formula of the podophyllotoxin derivative is as follows:

4. Use of a podophyllotoxin derivative according to claim 3 in the preparation of a drug for improving drug resistance of patients to breast cancer, Features: The resistance is caused by the endocrine therapy drug tamoxifen.

5. Use of a podophyllotoxin derivative according to claim 3 in the preparation of a drug for improving drug resistance of patients to breast cancer, Features: The breast cancer is ERα-positive breast cancer.

6. Use of a podophyllotoxin derivative and tamoxifen in the preparation of a drug for breast cancer, wherein the structural formula of the podophyllotoxin derivative is as follows:

7. Use of a podophyllotoxin derivative and tamoxifen according to claim 6 in the preparation of a drug for breast cancer, Features: The breast cancer is ERα-positive breast cancer.

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