[Anticancer effects of cytosine deaminase gene/5-fluorocytosine therapies to ovarian cancer in vivo].
OBJECTIVE
To evaluate the anticancer effects of cytosine deaminase (CD) gene/5-fluorocytosine (5-FC) to human ovarian papillary serous cystadenocarcinoma in nude mice.


METHODS
Replication-deficient adenovirus containing CD gene was used to transfect human embryonal kidney cell line 293, and the adenovirus's concentration was up to 1 x 10(10) pfu (plaque forming unit)/ml after purification. Ten female BULB/C nude mice were implanted subcutaneously with approximate 0.08 g tissue of ovarian papillary serous cystadenocarcinoma from the parental generation, and they were divided into test group and control group. While the tumors grew with diameter of approximate 3mm, test group received intratumoral injections of adenovirus-CD at 1 x 10(9) pfu in a 100 microl volume on day 1, 3, 5. These animals were administered 5-FC at doses of 400 mg/kg twice daily by intraperitoneal injection from day 1 to day 7. Normal saline was used in control group with the same volume and by the same methods. Tumor volumes were measured in following days.


RESULTS
(1) Compared with control group, the growth of tumors in test group was significantly suppressed. Twenty days after the therapies, the tumor volumes in test group and control group were (91 +/- 68) mm(3) and (238 +/- 122) mm(3) respectively, there was significant difference. This difference lasted for approximately 30 days (P = 0.045 - 0.019). (2) The mean time of tumor volume doubling in test group and control group were (8.1 +/- 0.7) days and (6.4 +/- 0.7) days, respectively (P < 0.05).


CONCLUSIONS
This research has shown the significant effects of CD gene/5-FC on human ovarian cancer in nude mice model. The results may be the important basis of clinical trials. They suggest that this toxic gene/prodrug therapy system may play an important role in ovarian cancer therapy in the future.
Department of Obstetrics and Gynecology, Second Affiliated Hospital of Sichuan University, Chengdu 610041, China.
Yuan
Y
Yao
Zhilan
Z
Peng
He
H
Wang
Qingli
Q
Li
Shanling
S
Liu
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D000963:Antimetabolites / Q000627:therapeutic use*; D043525:Cytosine Deaminase; D005260:Female; D005437:Flucytosine / Q000627:therapeutic use*; D015316:Genetic Therapy; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009700:Nucleoside Deaminases / Q000235:genetics*; D010051:Ovarian Neoplasms / Q000628:therapy*
D000963:Antimetabolites; D005437:Flucytosine; D009700:Nucleoside Deaminases; D043525:Cytosine Deaminase