A study of the RV-HSV-TK/GCV suicide gene therapy system in cervix cancer

Objective: To study in vitro and in vivo killing effect and the bystander effect of HSV-TK/GCV suicide gene system on human Cervix cancer cells Hela.Methods: GINaTK retroviral vector containing HSV-TK gene was transduced into PA317 packaging cell by lipofectin.Human Cervix cancer cell line Hela was infected by high titer viral supernatant.PCR was resorted to demonstrate the successful transduction of the HSV-TK gene.Hela/TK cells and Hela cells were used in in vitro and in vivo study.Results: PA317 cells were transfected successfully with HSV-TK gene by lipofectin(named PA317/TK).Experimental results revealed that stable virus producing cell line was established and Hela/TK cells expressing the HSV-TK gene were obtained successfully.In in vitro study,when the ratio of Hela/TK cells reached 10%,the tumor cell-killing proportion was almost 50 %.I In in vivo study,GCV could suppress tumor formation of the Hela/TK cells.After mice treated with GCV,the median tumor volume of mice implanted with Hela/TK+Hela(1:9)group,Hela/TK+Hela(1:1)and Hela/TK cells was respectively decreased to 88.9%(P0.001) and 69.4% and 52.8% compared with the control tumors.The expression of HSV-TK gene was detected by RT-PCR.Tumors treated with GCV revealed different histopathological features compared with the control tumors.Conclusion:The test showed that the HSV-TK gene can be transducted into Human Cervix cancer line Hela under the mediation of retrovirus and be stable expressed,HSV-TK/GCV suicide gene therapy system could improve the antitumoral efficiency.The bystander effect could be observated in HSV-TK/GCV system in in vitro and in vivo.