[Toxic effects of HSV-TK and CD-TK suicidal gene systems on prostate carcinoma cells].

ABSTRACT

BACKGROUND & OBJECTIVE: Suicidal gene therapy is one of promising gene therapies. In order to assess the value of suicidal gene therapy on human prostate carcinoma, the authors studied the toxic effects of HSV-TK gene and CD-TK fusion gene systems on prostate carcinoma cell line PC-3m. METHODS: HSV-TK gene and CD-TK fusion gene were separately transfected into PC-3m cells through retrovirus vectors. Reverse transcription-polymerase chain reaction (RT-PCR) was used to demonstrate successful transfection and transcription of suicidal genes. The toxic effects of GCV, 5-FC, and both of them on transfected PC-3m cells were explored by MTT assay; non-transfected PC-3m cells were used as control. RESULTS: Significantly cytotoxic activity of GCV was observed and 50% inhibitory concentration(IC(50)) was 8.34 microg/ml,the bystander effect of GCV was modest,while the bystander effect of 5-Fc was significant,it began to show when the percent of tansfected PC-3m cells in mixed cells was 5%. Simultaneous treatment with two prodrugs on CD-TK expressing cells resulted in additive or synergistic toxicity,coefficient of drug interaction(CDI) was under 1. CONCLUSION: CD-TK fusion suicidal gene system has significant toxic effect on PC-3m cells in vitro, which was superior to HSV-TK alone gene system.