[Antitumor effects of cytosine deaminase and HSV-tk double suicide gene with adenovirus mediation on rectal cancer cells].
OBJECTIVE
To study antitumor effects of cytosine deaminase (CD) gene/5-fluorocytosine (5-FC) and herpes simplex virus thymidine kinase(HSV-tk) gene/ganciclovir (GCV) systems on rectal cancer cells with adenovirus mediation.


METHODS
CD and HSV-tk double suicide genes were transinfected into HR-8348 rectal cancer cells with recombinant adenovirus mediation. The expression of CD and HSV-tk genes was detected with RT-PCR. Plating efficiency and MTT method were used to evaluate the antitumor effect of CD and 5-FC, HSV-tk and GCV systems.


RESULTS
Adenovirus was recombined with pAdCMV-Link1(CD + tk), pAdCMV-Link1(-), pAdCMV-Link1(CD), and pAdCMV-Link1(tk) plasmids respectively. HR-8348 cells were infected with the recombined adenovirus and the high expression of CD and (or) HSV-tk genes was found in the corresponding group of tumor cells. Before use of prodrug 5-FC and GCV, the plating efficiency and survival rate of the cells in each group were without significantly different (P > 0.05). But the plating efficiency and survival rate of the tumor cells in pAdCMV-Link1(CD + tk) transinfection group were more highly inhibited than in control, pAdCMV-Link1(-) (P < 0.01) and single suicide gene transinfection groups (P < 0.05) after use of 5-FC and GCV. Combined of use CD and 5-FC, HSV-tk and GCV systems remarkably inhibited the plating efficiency and growth of tumor cells transinfected with double suicide genes.


CONCLUSIONS
Transinfection of CD and HSV-tk double suicide genes has a powerful antitumor effect.
Li
S
S
Department of General Surgery, Beijing Military Area, General Hospital, Beijing 100700, China.
Yu
B
B
An
P
P
D000256:Adenoviridae / Q000235:genetics; D043525:Cytosine Deaminase; D015316:Genetic Therapy; D006801:Humans; D009700:Nucleoside Deaminases / Q000235:genetics*; D012004:Rectal Neoplasms / Q000473:pathology / Q000628:therapy*; D018139:Simplexvirus / Q000201:enzymology*; D013937:Thymidine Kinase / Q000235:genetics*; D014162:Transfection; D014407:Tumor Cells, Cultured
D013937:Thymidine Kinase; D009700:Nucleoside Deaminases; D043525:Cytosine Deaminase