Thioridazine Enhances The Action Of Cisplatin Against Chemoresistant Cancer Cells

ObjectiveTo explore in vitro effects of thioridazine(THD),alone or combined with cisplatin(DDP)on proliferation and apoptosis of cell line A549 and it’s chemoresistant subline A549/DDP.MethodsCells were divided into control,THD,DDP and THD+DDP groups.Cell viability was determined,and then apoptosis,cell cycle,mitochondrial membrane potential,and the activity of caspase 8 and caspase 9 were followed.The expression of Bax,Bcl-2,Caspase 3,RIP,Fas,Fas L and CHOP was assessed by Western blotting.ResultsTHD combined DDP can efficiently inhibit the proliferation of A549 and A549/DDP cells.THD combined DDP led to a higher percentage of apoptotic cells,a decrease of mitochondrial membrane potential,and activation of caspase 3,caspase 8 and caspase 9.Western blot demonstrated up-regulation of Bax,Fas,CHOP and RIP proteins,and down-regulation of the Bcl-2 protein.ConclusionTHD can induce cell death in chemoresistant cancer cells,and can enhance the action of DDP against sensitive and resistant cancer cells.