Objective       To evaluate the curative effect of Bifidobacterium infantis (BI)-mediated herpes simplex virus thymidine kinase (HSV-TK)/ganciclovir

(GCV) suicide gene therapy system on renal carcinoma in nude mice and investigate the effects of HSV-TK/GCV on renal carcinoma cells apoptosis and p-Stat3 and Bcl-xL expression.       Methods       The renal carcinoma model was established by subcutaneous injection of human renal carcinoma cell line 786-O into nude mice. The model mice were randomly divided into 4 groups

which were treated by intraperitoneal injection of GCV in combination with tail vein injection of normal saline (normal saline group)

BI (BI group)

BI carrying empty plasmid BI-pGEX-5x-1 (empty plasmid group)

and BI carrying recombinant plasmid BI-pGEX-TK (recombinant plasmid group). After 4 weeks treatment

tumor weights and nude mice weights were recorded. The apoptosis of renal carcinoma tissue cells was determined by TUNEL assay.The expression of p-Stat3

Bcl-xL protein was determined by immunohistochemical staining. The expression levels of Stat3

Bcl-xL mRNA and expression levels of p-Stat3

Bcl-xL protein were detected by real-time fluorescent quantitative PCR(real-time PCR) and protein imprinting method (Western blotting) respectively.       Results       After treatment

comparing with the empty plasmid group

the bifidobacterium infants group and the normal saline group

the nude mice weights of recombinant plasmid group increased(

P

0.05)

the tumor weights decreased(

P

0.05). TUNEL assay showed the apoptosis index of recombinant plasmid group was obviously higher than that of the empty plasmid group

the bifidobacterium infants group and the normal saline group(

P

0.01). Immunohistochemical staining showed that the expression of p-Stat3

Bcl-xL protein of recombinant plasmid group is significantly lower than that of the empty plasmid group

the bifidobacterium infants group and the normal saline group(

P

0.01). The expression levels of Stat3

Bcl-xL mRNA of recombinant plasmid group significantly lower than that of the empty plasmid group

the bifidobacterium group and the normal saline group(

P

0.01). the expr

ession levels of p-Stat3

Bcl-xL protein of recombinant plasmid group significantly lower than that of the empty plasmid group

the bifidobacterium group and the normal saline group(

P

0.01).      Conclusion       The BI-mediated HSV-TK/GCV suicide gene therapy system effectively inhibits nude mice renal carcinoma tumor growth

probably through inhibiting Stat3 activation and thereby blocking Stat3 signaling pathway

decreases the expression of its downstream antiapoptotic protein Bcl-xL

induces to nude mice renal carcinoma cells apoptosis

and thus plays a role of tumor suppression.