Study on Anti-Glioma Effect of Recombinant Adenovirus Mediated HSV-TK/ACV System Enhanced by wt-p53 Gene in vitro

Aim:To study the feasibility of enhancing anti glioma effect of suicide therapy (HSV TK/ACV) for malignant gliomas by cotransfection of wt p53 gene. Methods:AdCMV p53 was transfected into C6 glioma cells at MOI (Multiplicity of infection) of 0(A100),10(TPA), 100(TPA2), then AdCMV TK transducted C6 glioma cells of A100,TPA1 and TPA2 respectively at MOI of 100, the C6 glioma cells transducted by AdCMV p53 and AdCMV TK were exposed to various concentration of ACV. The cell survival rate was measured by MTT assay. Cell apoptosis was evaluated by TUNEL method. Expression of HSV TK gene was detected by in situ hybridization. Expression of exogenous p53 gene was identified by Western blot.Results:wt p53 significantly enhanced antitumor effect of HSV TK/ACV. The concentration of ACV for ID 50 (1 μg·ml -1 GCV) and ID 100 (10 μg·ml -1 ) of TPA2 cells was 10 times lower than that for the cells of TK ACV group (MOI=100).Apoptosis of C6 glioma cells can also be increased by cotransfecting with wt p53 gene.Conclusion:p53 gene transduction can significantly improve the anti glioma effect of HSV TK/ACV system in vitro.