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

Abstract

Abstract: 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% (P<0.01), 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 HSVTK GCV system in in vitro and in vivo.

Key words: gancyclovir, herpes simplex virus thymidine kinase (HSV-TK), breast cancer

CLC Number:

R737.33

JIANG Hong, HOU Chen-rong, CHEN Kao-shan, WANG Ming-ning, ZHANG Yu, WANG Wen-qing, YANG Sheng-xi. Experimental study of gancyclovir combining HSV-TK gene therapy system on breast cancer[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2008, 13(8): 856-859.

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