顺铂增强携带IL-24基因的双调控溶瘤腺病毒对结肠癌细胞株的杀伤作用

Cisplatin Can Increase the Anti-Colorectal Tumor Cell Lines Efficacy of Dual Regulated Oncolytic Adenovirus Mediate IL-24

研究端粒酶逆转录酶启动子hTERT启动子和缺氧反应元件HRE双调控的溶瘤腺病毒SG500-IL24联合化疗药物对人结肠癌细胞株的体外杀伤作用。采用MTT法检测病毒联合化疗对结肠癌细胞株HCT-116、SW620以及人正常细胞株L02增殖的抑制作用;利用Hoechst 33342染色对病毒-化疗疗法诱导的HCT-116细胞凋亡进行形态学观察;通过Western blot检测病毒-化疗疗法诱导的HCT-116细胞凋亡信号通路的变化。结果表明SG500-IL24或不携带外源基因的SG500联合低剂量的顺铂后,其对结肠癌细胞株HCT-116、SW620的杀伤作用显著提高(p<0.05);相同条件下对人正常细胞株L02无明显抑制作用。通过Western blot对联合疗法作用机制的初步探索表明,联合疗法增强caspase依赖性细胞凋亡通路的信号。

To study the combination effects of oncolytic adenovirus SG500-IL-24（double-regulated by hTERT promoter and HRE）and chemotherapy against human colorectal cancer cell lines in vitro. Methods： （1） To test the growth inhibition effects of combinational therapy on cancer cell lines HCT-116, SW620 and human normal cell line L02 by MTT assay; （2） after Hoechst 33342 dying, the apoptosis of HCT-116 induced by the viro-chemotherapy is observed under fluorescent microscope; （3） the changes in apoptosis signaling pathway are detected by Western blot. The kill effects of either SG500-IL24 or SGS00 are significantly improved when in combination of low does cisplatin（p〈0.05）, while the toxicity against normal cell line L02 is not apparent. Our primary study demonstrates that the combinational therapy achieves better therapeutic results through the up-regulation of caspase-dependent apoptotic signaling.