Synergistic Effect Of Tamoxifen And Simvastatin On MCF-7 Human Breast Cancer Cells And Related Mechanism

Background In the diagnosis of malignant tumors in American women,breast cancer accounted for the largest proportion.At present,the incidence of female breast cancer in China is similar to that in Europe and America.According to the expression of estrogen receptors in breast cancer cells,breast cancer can be divided into two categories.Breast cancer cells express estrogen receptors,whose disease progression depends on estrogen;breast cancer cells that do not express estrogen receptors,are not dependent on estrogen.The treatment of breast cancer has been the main direction of surgery,radiotherapy,chemotherapy,endocrine t herapy,targeted therapy,traditional Chinese medicine treatment,although has achieved good results,but it is difficult to obtain new results.Therefore exploring new treatment of breast cancer is very meaningful countermeasures and prospects.Tamoxifen is the first-line drug to treat the expression of estrogen receptor positive breast cancer patients,its advantage is the reliable curative effect and low side effect.Statins are commonly used in the prevention and treatment of cardio vascular diseases,which have been shown to be anti tumor in recent studies.Co mbination therapy is commonly used in the treatment of breast cancer,therefore,in this experiment,we investigated the possibility of the combination of two drugs in the treatment of breast cancer by observing the changes of cell proliferation inhibition,apoptosis and the expression of apoptosis related proteins in the combination of statins and Tamoxifen.Objective To investigate the combined effect of Tamoxifen(TAM)and Simvasta tin(SIV)on MCF-7 human breast cancer cells(MCF-7).Methods MTT assay assessed antiproliferative effects of TAM,SIV and Tam+S IV on growth of MCF-7 cells.Synergistic interaction between the two drugs was appraised by using the combination index(CI)method in vitro.The cell apoptosis morphological change was detected by the fluorescent microscope.The apoptosis of MCF-7 cells in the tamoxifen group,the simvastatin group and the tamoxifen + simvastatin group was detected by flow cytometry.The expression of Bcl-2and Bax was investigated by Western Blot.Results MTT assays indicated that the viability of MCF-7 was markedly reduced When SIV was combined with TAM compared to single drug treatment(CI<1).Furthermore,when SIV in combination with TAM exhibited a synergistic inh ibition of proliferation and induction of apoptosis in MCF-7.Moreover,the comb ination of TAM and SIV produced a stronger inhibitory effects on Bcl-2 and Bax expression than control or single drug treatment.Conclusion The combination of TAM and SIV can obviously increase the effect compared to single drug treatment,meaning that combination treatment may be a more effective therapy to breast cancer.