Experimental research on treating hepatic carcinoma by tram-arterial delivery of p53 gene mediated by lipsome combined transferring / 中华放射学杂志

ABSTRACT

Objective To investigate the trans-arterial delivery of p53 gene transfection efficiency and therapy effect on hepatic carcinoma in combination with transferrin mediated by liposome. Methods Twenty-five VX2 experimental rabbits were randomly divided into five groups, and the different doses of transferrin combined with p53-LipofectAMINE complex were delivered into the hepatic arteries of the VX2 hepatic carcinoma models. The tissue protein of the carcinoma was extracted after 48 h and the transfection efficiency and expression rate of p53 gene were analyzed by western blot and immune histochemical techniques, to inspect the expression proportion of p53 with different doses transferring. Another ten VX2 were divided into two groups, recombinant plasmid p53-LipofectAMINE complex and transferrin-p53-LipofectAMINE complex were delivered into the hepatic arteries in two groups respectively. The liver function, size of the tumor and survival time of the animals was compared between the two groups, and results were analyzed statistically. Results Semiquantitative analysis by Western Blot showed that the transfection and expression efficiency of p53 gene combined with transferrin were higher than those without it. By immune histochemieal techniques, the p53 gene's positive rate of highly expression with various doses of transferrin were found to be different, and there was remarkable difference between the groups with and without transferring. They were 58. 33%, 69. 44%, 80. 00%, 83.33%, 81.67% respectively, there was remarkable difference between the groups with and without transferring ( Totality x2 = 42. 37, P < 0. 01 ). The p53 gene's positive rate of expression increased gradually as the doses of transferrin increasing from 0 up to 200 μg, but the differences of positive rate had no statistical significance as the doses of transferrin increasing from 200 up to 400 μg ( x2 section 3 groups as former x2 = 4. 82, P < 0. 05,3 groups as latter x2 =0. 67 ,P <0. 05). There was no statistical difference in the liver function at points of time between VX2 rabbits with and without transferring. But the tumors' sizes had significant difference at various points of time. Conclusion Liposome-mediated p53 gene on treating hepatic carcinoma by trans-arterial gene delivery combined with transferrin is safe, and it can markedly enhance transfection efficiency and improve the therapy effect of p53 gene.