[The killing effects of two prodrug sensitivity genes on human pancreatic carcinoma cells PC-2].
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.


CONCLUSIONS
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.
Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100730.
L
L
Zhang
T
T
Liu
Q
Q
Cui
D002455:Cell Division / Q000187:drug effects; D043525:Cytosine Deaminase; D004926:Escherichia coli / Q000235:genetics; D005437:Flucytosine / Q000494:pharmacology*; D015774:Ganciclovir / Q000494:pharmacology*; D015316:Genetic Therapy; D009700:Nucleoside Deaminases / Q000494:pharmacology; D010190:Pancreatic Neoplasms / Q000473:pathology*; D011355:Prodrugs; D012190:Retroviridae / Q000235:genetics; D018139:Simplexvirus / Q000235:genetics; D013937:Thymidine Kinase / Q000494:pharmacology; D014162:Transfection; D014407:Tumor Cells, Cultured
D011355:Prodrugs; D005437:Flucytosine; D013937:Thymidine Kinase; D009700:Nucleoside Deaminases; D043525:Cytosine Deaminase; D015774:Ganciclovir