重组腺病毒ADV-TK对肝癌抑制作用的实验研究

目的观察已构建的含胸苷激酶（TK）自杀基因的重组腺病毒（ADV-TK）对肝癌细胞的体外杀伤作用和对肝癌裸鼠移植瘤的治疗效果。方法将ADV-TK体外感染人肝癌细胞株SMMC-7721,噻唑蓝（MTT）法检测受感染的SMMC-7721细胞被不同浓度更昔洛韦（GCV）作用后的细胞存活率情况。构建肝癌SMMC-7721裸鼠移植瘤模型,观察肿瘤注射重组腺病毒ADV-TK结合GCV治疗移植瘤的变化。结果相同滴度的重组腺病毒与不同浓度的GCV作用于肝癌细胞株SMMC-7721后,MTT法检测到细胞的存活率随着GCV浓度的增加而不断降低。动物实验中ADV-TK治疗组肿瘤体积明显小于对照组（ADV-null及NS）（P〈0.01）。结论重组腺病毒ADV-TK对肝癌SMMC-7721细胞的体外增殖和裸鼠体内的移植瘤生长均有明显的抑制作用。

Experimental Study on Gene Therapy for Liver Cancer via Recombinant Adenovirus Containing TK Gene

Objective To explore the inhibitory effect of recombinant adenovirus containing TK gene（ADV-TK）on transfected human liver cancer cells SMMC-7721 in vitro and murine transplanted hepatocarcinoma in vivo. Methods SMMC-7721cells transfected with ADV-TK were exposed to medium with GCV.The cell viability was measured by MTT assays.In the established model of SMMC-7721human liver cancer,nude mice underwent intratumoral injection with 1 109pfu ADV-TK,the control vector（ADV-null）or normal saline（NS）and again 7days later,twice for all.GCV was given at a dose of l00mg/（kg·d）on the following day of injection for 10days.The tumor inhibitory effect was observed by measuring the tumor sizes.Results After transfected by ADV-TKin vitro, and combined with GCV,the cell growth of SMMC-7721cell were significantly suppressed.The result of in vivo assay showed that tumor volumes in treatment group were apparently smaller than that in the control group（P 0.01）.Conclusion Recombinant adenovirus combined with GCV shows a significant inhibitory effect on SMMC-7721 cells in vitro and murine transplanted hepatocarcinoma in vivo.