Inhibitory Effect Of Thioridazine On Growth Of Gastric Cancer Cells And Its Mechanism

1. Objective: To studytheeffect of thioridazine on the apoptosis of gastric cancer cellsand its possible mechanism.2. Methods: To cultivate human gastric cancer SGC-7901 cells in vitro as the study abject. According to literature data and preliminary experiments gastric cancer SGC-7901 cells were cultured indifferent concentrations of thioridazine for 24 hours.2.1. MTT assay was used to detect inhibition rate. Gastric cancer SGC-7901 cells were cultured indifferent concentrations of thioridazine for 24 hours. MTT assay was used to examine the proliferation inhibition ofgastric cancer cells by thioridazine. Application of statistics to calculate the IC50(half maximal inhibitory concentration of a substance, IC50)。2.2. Observe cell morphology by use of microscope. Gastric cancer SGC-7901 cells were cultured indifferent concentrations of thioridazine for 24 hours. Then observe the morphology change of SGC-7901 cells with ordinary microscope.2.3. The expression of bax、bcl-2、caspase-3 were measured by Western blotting. Western blotting was used to detect the pro apoptosis protein Bax, caspase-3 and anti apoptosis protein Bcl-2 proteinexpressed level by SGC-7901 cells in different concentrations of thioridazine for 24 hours.2.4. Flow cytometry was used to determine the cell apoptosis. SGC-7901 cells were cultured indifferent concentrations of thioridazine for 24 hours. Then use flow cytometry to determine the cell apoptosis.3. Results:3.1. Thioridazine restrained the growth of gastric cancer obviously. The IC50 of MTT assay is 49.51±3.95μmol/L.3.2. Gastric cancer SGC-7901 cells were cultured indifferent concentrations of thioridazine for 24 hours. The cell volume and nucleus volume reduced, staining become weak, the number of cell nucleolus and pleomorphism reduce, partial cell no longer attaching and intercellular junction become loose were observed under microscope.3.3. Western blot showed concentration-dependant decrease in bcl-2 and increase inbax、caspase-3proteins. Each experimental group compared with the control group, the differences were statistically significant(P<0.05).3.4.Flow cytometry showedincrease of apoptosiswith the increase of thioridazine concentration.4 Conclusion:Thioridazine has obvious cytotoxic effect on gastric cancer.