Killing Effect Of Thioridazine On The Proliferation Of Breast Cancer Cells MDA-MB-231 And MCF-7

Background and Objectives Breast cancer is the most common malignancy in women. The incidence of breast cancer is increasing and dilinghua trend, especially triple-negative breast cancer(TNBC) that does not express ER,PR,Her-2 has a higher grade malignant, so how to find a way for new drugs against TNBC research becomes the focus of current breast cancer treatment[1-2]. Thioridazine is a phenothiazine derivative that widely used to treat serious mental and emotional disorder[3]. Recently research has proven that thioridazine has obviously anti-tumor cell activity in vitro, it may become an effective anti-tumor drug for tumor clinical treatment[4]. We detect the inhibition rate and apoptosis induced by thioridazine on breast cancer MDA-MB-231 and MCF-7cell and its mechanism.Methods The anti-proliferative effects of thioridazine on MDA-MB-231 and MCF-7 cells were measured with MTT and the values of IC50 were calculated. Flow cytometry was used to measure the cell cycle arresting and apoptosis. Caspase-3 activity assay kit was performed to detect Caspase-3 activity levels. The expression changes of the Bcl-2 and Bcl-xl were detected by western blot. Results After treated with thioridazine for 24 h, MDA-MB-231 and MCF-7 cells were significantly inhibited by the drug extracts. The values of IC50 were respectively 18 μmol/L and 22 μmol/L. Flow cytometry showed cells’ G0/G1 phase arrest along with an increase of apoptosis and intracellular Caspase-3 activity with the increase of thioridazine concentration. Western blot showed concentration-dependant decrease in Bcl-2 and increase in Bax proteins. Each experimental group compared with the control group, the differences were statistically significant(P<0.01). Conclusion Thioridazine has obvious cytotoxic effect on breast cancer cells MDA-MB-231 and MCF-7. It obviously induces breast cancer cells G0/G1 phase arresting and apoptosis, accompanied by up-regulation of Caspase-3 activity. The mechanism may be related to the down-regulation of Bcl-2 and up-regulation of Bax.