Effect Of CTAB On Drug Resistance And Apoptosis Of Breast Cancer Cells And Its Mechanism

Breast cancer is a fatal cancer in women.Currently,most frequently used strategy for therapy of breast cancer is still surgery combined with radiotherapy and chemotherapy.However,the adjuvent effect of chemotherapy on breast cancer is drug resistance,it is an unmet to develop novel therapeutical strategy for administration of breast cancer.Recent studies have shown that CTAB,as a small molecule compound,can inhibit cancer cell proliferation in a variety of tumors,but molecular mechanism underlying the inhibitory effect on breast cancer is still not clear,Therefore,this study intends to explore the regulatory effect of CTAB on breast cancer proliferation and drug resistance and explore its possible mechanism.In the first part of the study,we selected MCF-7/MDR,a breast cancer resistant cell line,and tested whether CTAB could increase the sensitivity of DOX to breast cancer by MTT method,the AMPK-HIF-P-gp signal pathway was detected by Western blot;Next,AMPK inhibitors and HIF over expression vectors were used to further prove the important role of AMPK and HIF in CTAB sensitization;At last,the model of subcutaneous transplanted tumor in nude mice was established to further prove the sensitization effect of CTAB in vivo,and to verify that CTAB regulates the drug resistance of breast cancer through AMPK-HIF-P-gp signal pathway,and to preliminarily explore the safety of CTAB.In the second part,we selected breast cancer cell line MCF-7 and used MTT method to detect whether CTAB has killing effect on breast cancer cells;Flow cytometry was used to detect its killing effect through apoptosis;Western blot was used to detect the expression of apoptosis related proteins such as p53,Bax,Bcl-2,P-bcl-2,Bim,Bad,Clevered Caspase-3 and Clevered Caspase-9,and to explore the possible mechanism of CTAB promoting apoptosis.Our study showed that safe dose of CTAB can increase the sensitivity of DOX to breast cancer,and this sensitization is achieved by activating AMPK and inhibiting HIF-1?.CTAB has certain safety.CTAB can promote the apoptosis of MCF-7 and MDA-MB-231 cells,and it is achieved by activating p53 and inhibiting Bcl-2.We then concluded that CTAB can induce the sensitivity of breast cancer cells to DOX chemotherapy by activating AMPK pathway,and CTAB may induce the endogenous apoptosis of mitochondria of breast cancer cells by activating p53 pathway.