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


CONCLUSIONS
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.
Zhang
Dong-Qing
DQ
Department of Urology, Qilu Hospital of Shandong University, Jinan, Shandong, 250012, PR China. zhang68dq@163.com
Xu
Chun-Xiao
CX
Xu
Zhi-Shun
ZS
Ma
Dao-Xin
DX
Zhang
Huai-Qiang
HQ
Liu
Chun-Sheng
CS
D045744:Cell Line, Tumor; D043525:Cytosine Deaminase / Q000235:genetics*; D005437:Flucytosine / Q000494:pharmacology; D015774:Ganciclovir / Q000494:pharmacology; D015316:Genetic Therapy; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000473:pathology / Q000628:therapy*; D011993:Recombinant Fusion Proteins / Q000235:genetics*; D018139:Simplexvirus / Q000201:enzymology*; D013937:Thymidine Kinase / Q000235:genetics*
D011993:Recombinant Fusion Proteins; D005437:Flucytosine; D013937:Thymidine Kinase; D043525:Cytosine Deaminase; D015774:Ganciclovir