Effect of salinomycin on cisplatin resistance of human nasopharyngeal carcinoma cells CNE2/DDP and its mechanisms

CHEN Dongjie; LIAO Xueyang; CHEN Kexu; LI Yibin; WANG Senming

doi:10.3969/j.issn.1002-266X.2016.48.006

Abstract：Objective To investigate the effect of salinomycin on the cisplatin resistance of human nasopharyngeal carcinoma CNE2/DDP ceils and its possible mechanisms.Methods CNE2/DDP ceils were randomly divided into four groups,which were separately treated with 2 μg/mL cisplatin (cisplatin group),8 μmmol/L salinomycin (salinomycin group),8 μ mmol/L salinomycin + 2 μg/mL cisplatin (combination group) and 0.1％ DMSO (control group).Inhibitory rate of proliferation was assessed by the Cell Counting Kit 8.Apoptosis rate was measured by flow cytometry.Caspases3 and caspase9 activity was assessed by a colorimetric assay utilizing specific substrates.The protein expression of Wnt/β-catenin signaling pathway (β-catenin and p-LRP6) as well as mTORc1 signaling pathway (P70S6K,p-P70S6K,S6,and p-S6) was evaluated by Western blotting.Results Compared with the control group,the inhibitory rate,apoptosis rate,Caspase-3/9 activity were increased in the cisplatin group,salinomycin group,and combination group (all P ＜ 0.05).Indexes mentioned above were increased the most in the combination group while salinomycin group ranked the second and cisplatin group ranked the third (all P ＜ 0.05).The expression of β-catenin,p-LRP6,p-P70S6K,and p-S6:the salinomycin group and combination group was decreased as compared with the cisplatin group and control group (all P ＜ 0.05).Meanwhile,no significant differences were found between salinomycin group and combination group as well as between the cisplatin group and control group (all P ＞ 0.05).No significant difference was found in the expression of P70S6K and S6 between these four groups (all P ＞ 0.05).Conclusion Salinomycin can reverse the cisplatin resistance of human nasopharyngeal carcinoma cells CNE2/DDP which is possibly mediated by improving caspases activity and inhibiting both Wnt/β-catenin signaling pathway and mTORC1 signaling pathway.