Effect Of HSV-tk/GCV Mediated By Bifidobcterium Infantis On Treatment Of Renal Cell Carcinoma And Activity Of Nuclear Factor Kappa B In Nude Mice

Objective: To confirm Bifidobacterium infantis mediated herpessimple virus thymidine kinase/ganciclovir suicide gene system on thetreatment of renal cell carcinoma in nude mice, and detect the effect ofinduction of apoptosis and expression of nuclear factor kappa B signalingpathway in renal cell carcinoma.Methods: Cultured tumor cells which obtained through digestion ofsubcutaneous tumor, and then subcutaneously injected into the right flank ofthe test mice. The animals were randomly divided into four groups:BI-pGEX-TK/GCV treatment group (recombinant plasmid group),BI-pGEX-5X-1/GCV group (empty plasmid group), BI/GCV group (emptyBI group) and normal saline/GCV control group (normal saline group).Either saline or drugs was injected through tail vein, followed withintraperitoneal injection of GCV. The quality of life was recorded after4weeks treatment, tumor weight was also evaluated. Apoptosis of tumor wasdetected by TUNEL assay. Expressions of Rel A and Caspase-3were assessed through qPCR and western blot.Results: The quality of life of recombinant plasmid group was betterthan empty plasmid group, empty BI group and normal salinegroup(p=0.006<0.01), in addition, the tumor weight of recombinant groupwas significantly lower(p=0.003<0.01). Although different degrees ofapoptosis in tumor cells from each group were detected by TUNEL assay,recombinant plasmid group exerted stronger apoptotic response in tumorcells than did the other three groups after ganciclovir(GCV)treatment(p=3.46113E-07<0.01). More importantly, qPCR and western blotfurther demonstrated that the recombinant plasmid group had the highestlevel of Caspase-3gene and protein expressions than empty plasmid group,empty BI group and normal saline group(p=1.27303E-07<0.01), in contrast,the level of Rel A gene and protein expressions waslowest(p=5.65095E-09<0.01).Conclusion: Bifidobacterium infantis-mediated HSV-TK/GCV suicidegene therapy system possibly by affecting the NF-KB signaling pathway toinduce apoptosis of tumor cells in renal cell carcinoma, which play a tumorsuppressor role.