盐霉素联合奥沙利铂对PANC89的增殖及诱导凋亡的机制  

Salinomycin combined with oxaliplatin inhibits proliferation and induces apoptosis of human pancreatic cancer cell line PANC89

作　　者：何磊[1] 王凡[1] 戴维其 程萍[1] 沈淼[1] 郭传勇[1] 

机构地区：[1]同济大学附属第十人民医院消化内科,上海200072

出　　处：《同济大学学报（医学版）》2013年第6期6-11,共6页Journal of Tongji University(Medical Science)

基　　金：国家自然科学基金(81302063)

摘　　要：目的研究盐霉素对人胰腺癌细胞株PANC89的增殖及诱导凋亡的影响及其联合奥沙利铂后增敏其抗肿瘤的作用及机制。方法采用CCK-8法及Hoechst 33342染色法,分别检测盐霉素及盐霉素联合奥沙利铂对PANC 89细胞生长的抑制、凋亡的影响;并且用流式细胞术检测细胞凋亡率。Real-time PCR和Western blot用于分析盐霉素处理后相关基因的mRNA和蛋白表达水平。结果盐霉素抑制PANC 89的增殖,且可增敏奥沙利铂抗胰腺癌作用;经过盐霉素联合奥沙利铂处理后,胰腺癌细胞的凋亡率增加(P<0.05)。经盐霉素以及联合奥沙利铂作用后Bax、Bak的表达明显增加,而Bcl-2及Bcl-x及β-catenin and p-GSK-3β的表达亦被明显抑制(P<0.05)。结论盐霉素可抑制PANC 89的增殖,增敏奥沙利铂的抗肿瘤作用,通过Bcl-2途径诱导人胰腺癌细胞株PANC89的凋亡,并且这可能是通过对Wnt/β-catenin通路的抑制产生的。Objective To investigate the anti-tumor effect of salinomycin combined with oxaliplatin on human pancreatic cancer cell line PANC89 and its possible mechanisms. Methods The inhibitory effect of salinomycin, and salinomycin plus oxaliplatin on cell growth of PANC89 was tested by CCK- 8 assay. Hoechst33342 staining was used to observe cell apoptosis. The rate of apoptosis was tested by flow cytometry. Real-time PCR and Western blot were used for analysis of mRNA and protein expression levels of Bcl-2 family and β-catenin and GSK-3β, the key genes of the Wnt/beta-catenin pathway. Results Salinomycin inhibited the growth of PANC89 cells in a dose-dependent manner. Salinomycin increase the effect of oxaliplatin in vitro. After treatment of PANC89 cells with salinomycin or combined with oxaliplatin, the apoptosis of pancreatic cancer cells significantly increased compared to the control group. The expression of Bax and Bak was significantly increased and the expression of Bcl-2 and Bcl-xl was significantly inhibited, while the expression of β-catenin and p-GSK-3β was also significantly inhibited. Conclusion Salinomycin inhibits the proliferation of PANC89 ceils and enhances the anti-tumor effect of oxaliplatin and induces the apoptosis, which may be via Bcl-2 and the inhibition of Wnt/β-catenin pathway.

关 键 词：盐霉素 胰腺肿瘤 利铂 细胞凋亡 WNT β-catenin通路 

分 类 号：R735.9[医药卫生—肿瘤]