腺病毒介导p16基因表达对胃癌细胞化疗敏感性的增强作用

Adenovirus-mediated p16 expression enhances chemotherapeutic sensitivity of gastric cancer cells

目的研究p16基因对胃癌细胞化疗敏感性的作用。方法构建携带p16基因的腺病毒感染胃癌细胞株SGC-7901;Western blotting鉴定癌细胞p16的表达;MTT法检测顺铂(DDP)对癌细胞存活率的影响;动物体内实验验证p16与DDP对癌细胞生长抑制的协同作用。结果腺病毒感染胃癌细胞后表达p16使癌细胞对DDP更为敏感,其中p16阳性组的细胞在DDP浓度达到1.5mg/L时,细胞存活率降至20%以下,而同期p16阴性组的细胞在相同DDP浓度时存活率仅下降至60%左右。p16腺病毒联合DDP对裸鼠移植瘤的生长抑制明显强于单独应用p16腺病毒或DDP。结论胃癌细胞获得外源性p16表达对DDP的敏感性提高,p16基因治疗联合化疗将有可能提高抗肿瘤效果。

Objective To investigate the effect of p16 gene on chemotherapeutic sensitivity of gastric cancer cells. MethodsAdenovirus-armed p16 gene was constructed and used to infect gastric cancer cell line SGC-7901.Western blotting was used to detect p16 expression,MTT assay was used to examine the viability of cancer cells after treatment with cisplatin（DDP）.The antitumor effect of p16 combined with DDP was proved in xenografts in nude mice. Resultsp16 re-expressed after infection with adenovirus carrying p16 gene.The cancer cells with p16 positive expression were sensitive to DDP,and the viability of p16-positive cancer cells was decreased below 20% when the concentration of DDP was 1.5mg/L,whereas the viability of p16-negative cancer cells was about 60%.The inhibition effect of p16 with DDP on cancer growth in nude mice was stronger than that of p16 or DDP. ConclusionGastric cancer cells obtained p16 re-expression were more sensitive to DDP,demonstrating that p16 gene therapy in combination with chemotherapy may improve the efficacy of cancer treatment.