17-DMAG与奥沙利铂对结直肠癌细胞增殖和侵袭的协同抑制作用  

Co-inhibition effect of 17-DMAG and oxaliplatin on proliferation and invasion of colorectal cancer cells

作　　者：周建平[1] 王维民[1] 邓建良[1] 周炎[1] 吴露露[1] 郭治源[1] 史建能 史俊[1] 周苏君[1] 徐泽宽[2] 

机构地区：[1]江苏大学附属宜兴医院胃肠外科,214200 [2]南京医科大学第一附属医院普通外科

出　　处：《中华胃肠外科杂志》2015年第4期370-375,共6页Chinese Journal of Gastrointestinal Surgery

基　　金：江苏大学医学临床科技发展基金（JLY2010044）;国家自然科学基金面上项目（81072031）;国家自然科学基金面上项目（81272712）;国家基金国际合作项目（812111519）

摘　　要：目的：探讨热休克蛋白90的抑制剂17-DMAG与奥沙利铂对结直肠癌细胞增殖和侵袭的影响。方法17-DMAG、奥沙利铂和两药剂量减半联用处理处于对数生长期的结肠癌细胞株SW480和HCT116后，用CCK8试剂检测细胞增殖活力，用RT-PCR和Western blot检测相关凋亡基因的表达，用Transwell趋化实验检测细胞侵袭能力。结果17-DMAG和奥沙利铂处理结直肠癌细胞后，细胞生长均受到抑制（P＜0．05），且该抑制作用呈现时间和浓度依赖性。当用17-DMAG 100 nmol／L、奥沙利铂50 mg／L和两药剂量减半联用分别处理结直肠细胞时，反转录PCR结果显示，凋亡抑制基因（Bcl-2）的mRNA表达均降低（均P＜0．05），凋亡促进基因（Bax）的mRNA表达均增高（均P＜0．05）；Western blot结果显示，PARP-1的89 kD剪切体表达水平均增加；且两药减半联用时上述变化更加明显。 Transwell趋化实验显示，奥沙利铂联合17-DMAG降低肿瘤细胞透膜百分比的效果明显优于单一用药（均P＜0．01），且转移相关分子MMP9和整合素β3表达明显低于单药。结论17-DMAG与奥沙利铂能够协同抑制结直肠癌细胞生长和侵袭。Objective To explore the effect of heat shock protein 90 （HSP90） inhibitor （17-DMAG） and oxaliplatin on the proliferation and invasion of colorectal cancer. Methods After 17-DMAG, oxaliplatin and half-dose combination of 2 drugs processing colorectal cancer SW480 and HCT116 cell lines, CCK8 assay was applied to detect cell viability. RT-PCR and Western blot were used to detect the expression level of the apoptosis-related molecules. Transwell chemokine axis experiment and Western blot were employed to detect cell invasion ability and the expression level of tumor metastasis-associated protein. Results The growth of SW480 and HCT116 cells was inhibited after the administration of 17-DMAG and oxaliplatin （P〈0.05） in dose- and time-dependent manner. Processed by 17-DMAG 100 nmol/L, oxaliplatin 50 mg/L and half-dose combination of 2 drugs, transcription level of the apoptosis inhibitory gene （Bcl-2） in SW480 and HCT116 cells was decreased, the level of apoptosis promoting gene （Bax） transcription and protein PARP-1 spliceosome expression was increased, and the above trend was more obvious when using half-dose combination of 2 drugs. Transwell chemokine axis experiments showed the penetrating relative percentage and expression level of MMP9 and integrin β3 decrease d, especially for half-dose combination of 2 drugs. Conclusion 17-DMAG and oxaliplatin can co-inhibit the proliferation and invasion of colorectal cancer.

关 键 词：结直肠肿瘤 热休克蛋白 奥沙利铂 增殖 转移 

分 类 号：R735.34[医药卫生—肿瘤]