双歧杆菌介导HSV-tkGCV治疗大鼠膀胱癌的实验研究.docVIP

双歧杆菌介导HSV-tk/GCV治疗大鼠膀胱癌的实验研究( 殷祥瑞,唐伟,喻备,王亚荣(400016 重庆，重庆医科大学附属第一医院泌尿外科) [摘要]：目的 观察双歧杆菌介导的单纯疱疹病毒胸苷激酶(HSV-)/丙氧鸟苷(GCV)[关键词]：基因治疗；HSV-tk/GCV；双歧杆菌；细胞色素C；半胱氨酸天冬氨酸蛋白酶9 [中图法分类号] R730.5 [文献标志码] A HSV-tk/GCV gene therapy mediated by bifidobacterium for bladder cancer in a rat model Yin Xiangrui, Tang Wei, Yu Bei, Wang Yarong (Department of Urology, First Affliated Hospital, Chongqing Medical University, Chongqing, 400016, China) [Abstract] Objective To observe the effect of Herpes Simplex Virus Thymidine kinase/ganciclovir (HSV-tk/GCV) gene therapy mediated by bifidobacterium for bladder cancer in a rat model and explore the possible mechanism. Method We established a rat model of bladder tumors, which was induced by N-methyl-nitrosourea perfushion and divided randomly into three groups: saline control group(group A); bifidobacterium/PGEX-5X-1 control group(group B), bifidobacterium/PGEX-tk treatment group(group C). After treatment, we contrasted the weight of each group and detected the apoptosis of each group by TUNEL method. The expression of cytochrome c and caspase-9 in bladder tumor tissue samples of each group were tested by reverse transcription polymerase chain reaction (RT-PCR) and Western blotting at mRNA and protein levels, respectively. Results The weight of group C was lower significantly than that in group A and group B(P0.001,P=0.000). While various degrees of apoptosis of tumor cells were detected in all groups using in situ TUNEL assay, apoptosis was mostly notable in group C. The mRNA and protein expression levels of cytochrome c and caspase-9 in group C were higher than those in group A and group B(P0.001,P=0.000).Conclusion A Bifidobacterium-mediated HSV-tk/GCV gene therapy system exhibits antitumor activity in a rat model of bladder cancer. The therapy system induces apoptosis may via upregulated cytochrome c and activated caspase-9. [Key words] gene therapy; HSV-tk/GCV; bifidobacterium; cytochrome c; caspase-9 Corresponding author: Tan