Objective: To compare the killing effects of herpes simplex virus thymidine kinase (HSV-TK)/ganciclovir (GCV) system versus cytosine deaminase (CD)/5-fluorocytosine (5-FC) system on human pancreatic carcinoma PC-2 cells.
Methods: Recombinant retroviral vectors expressing HSV-TK and CD genes were constructed and transduced into pancreatic carcinoma cell line. Prodrug sensitivity and IC50 values (concentration of drug at which cell growth is inhibited by 50%) of the transduced cells were measured by MTT method. The bystander effects in the two systems were also compared.
Results: The IC50 value of HSV-TK-transduced cells to GCV was (1.06 +/- 0.12) micromol/L and 558-fold lower than parental PC-2 cells, while the IC50 value of CD-transduced cells to 5-FC.00 was (33.00 + 0.95) micromol/L and 258-fold lower than parental PC-2 cells. Mixed cells containing 10% of transduced cells showed 39% and 50.3% growth inhibition in TK/GCV and CD/5-FC systems respectively.
Conclusion: Both HSV-TK/GCV and CD/5-FC systems showed effective antitumor activity in vitro to pancreatic carcinoma PC-2 cells. The therapeutic index of HSV-TK/GCV system is higher, but its bystander effect is lower than that of CD/5-FC system.