Experimental study of gancyclovir combining HSV-TK gene therapy system on breast cancer

AIM: To study the killing effect and the bystander effect of gancyclovir(GCV) combining herpes simplex virus thymidine kinase (HSV-TK) gene therapy system on human breast cancer cells. METHODS: GINaTK retroviral vector containing HSV-TK gene was transduced into PA317 packaging cell by liposome transfection method. The human breast cancer cell line was infected by high titer viral supernatant. MA782/5S-8102/TK cells and MA782/5S-8102 cells were used in in vitro and in vivo study. RESULTS: Experimental results revealed that in in vitro study when the cell population ratio of MA782/5S-8102/TK cells reached 10% the tumor cell-killing proportion was almost 50%, in in vivo study GCV could suppress tumor formation of the MA782/5S-8102/TK cells. After treated with GCV, the median tumor volume of mice implanted with MA782/5S-8102/TK+MA782/5S-8102 (19) group MA782/5S-8102/TK+MA782/5S-8102(11) and MA782/5S-8102/TK cellswas respectively decreased by 11.1%(P0.01), 30.6% and 47.2% compared with the control tumors. Tumors treated with GCV revealed different histopathological features compared with the control tumors. CONCLUSION: The HSV-TK gene could be transducted into human breast cancer line under the mediation of retrovirus and be stable expressed, HSV-TK/GCV 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.