HSV-TK/GCV Gene Therapy Mediated By Bifidobacterium For Bladder Cancer In A Rat Model

Objective: To observe the effect of Herpes Simplex Virus Thymidinekinase/ganciclovir (HSV-tk/GCV) gene therapy mediated bybifidobacterium for bladder cancer in a rat model and explore the possiblemechanism.Method: We established a rat model of bladder tumors, which wasinduced by N-methyl-nitrosourea perfushion and divided randomly intothree groups: saline control group(group A); bifidobacterium/PGEX-5X-1control group(group B), bifidobacterium/PGEX-tk treatment group(groupC). After treatment, we contrasted the weight of each group and detectedthe apoptosis of each group by TUNEL method. The expression ofcytochrome c and caspase-9in bladder tumor tissue samples of each groupwere 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 ingroup A and group B(P<0.001,P=0.000). While various degrees ofapoptosis of tumor cells were detected in all groups using in situ TUNEL assay, apoptosis was mostly notable in group C. The mRNA and proteinexpression levels of cytochrome c and caspase-9in group C were higherthan those in group A and group B(P<0.001,P=0.000).Conclusion: A Bifidobacterium-mediated HSV-tk/GCV gene therapysystem exhibits antitumor activity in a rat model of bladder cancer. Thetherapy system induces apoptosis may via endogenous apoptosis pathway.