Combination Of Salinomycin And Arsenic Trioxide Eliminates Renal Cancer KCC853 Cell

Objectives:To study the antitumor effect and mechanisms with salinomycin and arsenic trioxide on human renal cancer KCC853 cell lines in vitro.Further observation of the inhibitory effect of salinomycin and arsenic trioxide on the growth of human renal carcinoma KCC853cells in nude mice in vivo.Methods:?1?MTT assay was used to detect the inhibitory effect of salinomycin and arsenic trioxide on the proliferation of KCC853 cells;?2?For single agent and combined medication,the effects on the biological behaviors of renal cancer KCC853 cell using cell colony test,cell scratch test,Hoechst 33258 staining method and flow cytometry,respectively.?3?The orthotopic tumor model was used to investigate the inhibition effects of salinomycin and arsenic trioxide on KCC853 tumor growth in vivo.Results:?1?Salinomycin and arsenic trioxide can availably inhibit the growth of KCC853 cell lines,the maximal inhibitory effect?Imax?of salinomycin was 98.95%,the half-effect inhibition concentration?IC50?was 14.61?g/ml.The maximal inhibitory effect?Imax?of arsenic trioxide was was 94.49%,the half-effect inhibition concentration(IC₅₀)was1.13?g/ml.?2?Low doses of salinomycin and arsenic trioxide could inhibit the proliferation and migration of KCC853 cells,significantly.In the colony inhibition experiments,the inhibition rates of salinomycin and arsenic trioxide on KCC853 cells were 37.23%and 43.83%,respectively,and the inhibition rate of colony-forming cells was 57.50%in combination group,and the combination group was more effective?P<0.05?.?3?Hoechst33258 staining showed that,compared with the control group,salinomycin and arsenic trioxide groups,the number of cells decreased,the cell apoptosis,the nucleus showed dense infection;compared with the single drug group,the combination group apoptosis of the cells more obvious.?4?The effect of salinomycin and arsenic trioxide on KCC853 cell apoptosis and mitochondrial membrane potential were analyzed by flow cytometry.The apoptotic rates of KCC853 cells induced by salinomycin and arsenic trioxide were 12.05%and 26.77%,respectively,and the apoptotic rates were 49.01%in combination group,and the combination group was more effective?P<0.05?.Salinomycin and arsenic trioxide resulted in a decrease of mitochondrial membrane potential of 20.54%and 25.96%,respectively,compared with 46.26%in the combination group,which was more significant than that of the single drug group?P<0.05?.?5?Salinomycin and arsenic trioxide can inhibit the growth of nude mice orthotopic tumor significantly,the inhibitory rates of salinomycin and arsenic trioxide were 40.74%and 44.44%,respectively,and the inhibition rate was 49.15%in combination group?P<0.05?.Conclusion:?1?Salinomycin and arsenic trioxide have a significant inhibitory effect on KCC853 cells in a concentration-dependent manner?2?Low doses of salinomycin and arsenic trioxide could inhibit the proliferation and migration of KCC853 cells,significantly,and promote it apoptosis.?3?Salinomycin and arsenic trioxide can inhibit the growth of nude mice orthotopic tumor significantly.