The Antitumor Effect of Suicide Gene Therapy Using Bifidobacterium infantise-mediated Herpes Simplex Virus Thymidine Kinase/Ganciclovir in a Nude Mice Model of Renal Cell Carcinoma

作者：Xiao, Xiao; Jin, Ren; Li, Jiang; Bei, Yu; Wei, Tang^*

来源：Urology, 2014, 84(4): 982.e15-982.e20.

DOI：10.1016/j.urology.2014.05.020

• SELECTIVE LOCALIZATION
• DELIVERY-SYSTEM
• BLADDER-CANCER
• RAT MODEL
• KAPPA-B
• GROWTH
• TUMOR
• TRAIL
• DEATH
• EXPRESSION

OBJECTIVE To confirm the effectivity of Bifidobacterium infantis-mediated herpes simplex virus thymidine kinase/ganciclovir suicide gene system on the treatment of renal cell carcinoma in nude mice and further explore the mechanisms. @@@ MATERIALS AND METHODS A B infantis thymidine kinase (B infantis-TK) suicide gene system was constructed in our previous study. Tumor-bearing nude mice were randomized into 4 groups and injected with normal saline, B infantis, B infantis/pGEX-1 lambda T, and B infantis-TK, respectively, via tail vein, followed by intraperitoneal injection of ganciclovir. The treatment effects were evaluated by the terminal deoxynucleotidyl transferase-mediated deoxynucleotide triphosphate nick end labeling assay, quantitative reverse transcriptase polymerase chain reaction, and Western blotting. Side effects were also recorded. @@@ RESULTS Compared with the other 3 treatments, the treatment with B infantis-TK resulted in a significant effective antitumor activity and stronger apoptotic response. Western blot analysis showed that the expression levels of Rel A and Bcl-xL were significantly lower, whereas those of caspase 3 and Bax were significantly higher in tumor tissues resected from group B infantis-TK, which were consistent with the quantitative reverse transcriptase-polymerase chain reaction results. @@@ CONCLUSION The B infantis-TK/ganciclovir therapy system exhibits an effective antitumor activity by promoting tumor cell apoptosis through both the intrinsic and the extrinsic apoptotic pathways.

• 出版日期2014-10
• 单位成都大学; 重庆医科大学