Sensitization of prostate cancer cell lines to 5-fluorocytosine induced by adenoviral vector carrying a CD transcription unit.
OBJECTIVE
To investigate the efficiency of the cytosine deaminase adenoviral/5-fluorocytosine system on prostate cancer cell lines.


METHODS
We used cell culture, infectivity and sensitivity tests, to observe bystander effect by animal tests.


RESULTS
Established prostate cancer cell lines are eventually infectible by adenoviral vector. The ratio of vector/cell at which infection occurs depends on the specific cell line. The peak of expression of the transferred cytosine deaminase gene occurred in cells at different time, but persisted beyond 11 days. These prostate cell lines are sensitized to 5-fluorocytosine by infection with adenoviral vector carrying the cytosine deaminase gene. Only 5% of the LNCap and 10% of the RM-1 cells were infected and produced 100% cell death. In the animal test, there was significant inhibition of tumor growth at a ratio of 400 vector particles/cell with the systematic treatment of 5-fluorocytosine.


CONCLUSIONS
Adenoviral vector carrying a cytosine deaminase transcription unit can sensitize prostate cancer cell lines to 5-fluorocytosine. The system can significantly inhibit the growth of prostatic tumors in mice.
Yin
L
L
Department of Pathophysiology, Shanghai Medical University, Shanghai 200032, China. lhyin@shmu.edu.cn
Fu
S
S
Wang
X
X
Nanakorn
T
T
Won
J
J
Deisseroth
A
A
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D000963:Antimetabolites / Q000494:pharmacology*; D024201:Bystander Effect; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D043525:Cytosine Deaminase; D004305:Dose-Response Relationship, Drug; D005437:Flucytosine / Q000494:pharmacology*; D015870:Gene Expression; D005822:Genetic Vectors / Q000235:genetics; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009368:Neoplasm Transplantation; D009700:Nucleoside Deaminases / Q000235:genetics* / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D013997:Time Factors; D014158:Transcription, Genetic; D014162:Transfection; D019076:Transgenes / Q000235:genetics; D014407:Tumor Cells, Cultured / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
D000963:Antimetabolites; D005437:Flucytosine; D009700:Nucleoside Deaminases; D043525:Cytosine Deaminase