A Study of the RV-HSV-TK/GCV Suicide Gene Therapy System in Breast Carcinoma

Objective To study the killing effect in vitro and in vivo and the bystander effect of HSV-TK/GCV suicide gene system on mice breast carcinoma cells MA782/5S-8102. Methods GINaTK retroviral vector containing HSV-TK gene was transduced into PA317 packaging cell by lipofectin.Mice breast carcinoma cell line MA782/5S-8102 was infected by high titer viral supernatate. PCR Was resorted to demonstrate the successful transduction of the HSV-TK gene. MA782/5S-8102 /TK cells and MA782/5S-8102 cells were used in study in vitro and in vivo study. Results PA317 cells were transfected successfully with HSV-TK gene by lipofectin(named PA317/TK). The results revealed that stable virus producing cell line was established and MA782/5S-8102/TK cells expressing the HSV-TK gene were obtained successfully. In vitro, when the ratio of MA782/5S-8102 /TK cells reached to 10%,the tumor cell-killing proportion was almost 50%. In vivo, GCV could suppress tumor formation of the MA782/5S-8102/TK cells. Tumors treated with GCV revealed different histopathological features compared with the control tumors. The expression of HSV-TK gene was detected by RT-PCR. Conclusion The test showed that the HSV-TK gene can be transducted into mice breast cancer line MA782/5S-8102 under the mediation of retrovirus and be stable expressed, HSV-TK/GCV suicide gene therapy system could improve the antitumor efficiency. The bystander effect could be observed in HSV-TK/GCV system in vitro and in vivo.