Effect of p53 gene transfection on human hepatocarcinoma cells' sensitivity to irradiation.

Abstract

e22018 Background: Several studies demonstrated that p53 gene transfection enhanced the anti-tumor effects of radiotherapy. This study is to investigate whether p53 gene transfection can increase the radiosensitivity of liver tumor cells. Methods: Liver tumor cell lines, HepG2 (with wild type p53 genes) and PLC/PRF/5 (with mutant p53 genes), were separately transfected with recombinant adenoviral human p53 gene (rAdp53) and adenoviral enhance green fluorescent protein gene (AdEGFP), forming 4 types of cells: HepG2 transfected with rAdp53, HepG2 with AdEGFP, PLC/PRF/5 with rAdp53, and PLC/PRF/5 with AdEGFP. The transfected and untransfected HepG2 and PLC/PRF/5 cells were irradiated with 6MV-X at doses of 0, A2, A4, A6, A8, A and 10 Gy. After exposition to radiation, cell survival, clonogenic capacity, and apoptosis were analyzed. The effect differences between cell types were analyzed using statistical methods of pairwise group comparisons and mixed effect model. Results: After exposing irradiation, all the cells’ survival rate and clonogenic capacity decreased, and the proportion of apoptotic cell increased. These effects become stronger with increaseing dose of radiation. Between untransfected cells, radiation had a stronger effect on HepG2 cells than PLC/PRF/5 and the differences were statistically significant for all the 3 measures. The rAdp53 transfection, not the AdEGFP, significantly enhanced radiation effects on both cell lines. The enhanced effects on PLC/PRF/5 cells were significantly stronger then the enhanced effects on HepG2 cells. Conclusions: PLC/PRF/5 cells with mutant p53 genes were more resistant to radiation then HepG2 with wide type of p53 genes. The rAd-P53 transfection could enhance radiosensitivity of both cell lines, but the enhanced effect on PLC/PRF/5 cells with mutant p53 gene was stronger than HepG2 with wide type of p53 genes.