Anti glioma effect of recombinant adenovirus mediated HSV TK GCV system optimized by wt p53 gene transfer in vivo

Objective To study the feasibility of optimizing anti glioma effect of suicide gene therapy (HSV TK GCV) for malignant gliomas by wt p53 in vivo. Methods Rat glioma model was established by injecting 5×10 5 C6 glioma cells into the right caudate nucleus of SD rats. adCMV p53 and adCMV TK were respectively injected into glioma on day 5 and 6. On day 7, ganciclovir(GCV) was administrated intraperitoneally at 15 mg·kg -1 ·d -1 for 14 days. The survival time of all rats were observed. Intracerebral tumors were monitored dynamically by enhanced MRI. Cell apoptosis was evaluated by TUNEL method. Results Wt p53 significantly enhanced antitumor effect of HSV TK GCV. The survival time of rats with glioma and apoptosis of C6 glioma cells was increased. Enhanced MRI showed that intracranial tumor treated by p53+HSV TK and half dose of GCV disappeared within 4 weeks. Conclusions It may be more optimal for clinical therapeutic trials of suicide gene therapy by combining HSV TK GCV with p53 for malignant gliomas.