Gene therapy for ovarian cancer using adenovirus-mediated transfer of cytosine deaminase gene and uracil phosphoribosyltransferase gene directed by MDR1 promoter.
OBJECTIVE
To evaluate the specific killing effects of the adenoviral vector in which the CD::UPP genes were directed by the MDR1 promoter on Taxol-resistance ovarian cancer cells in vitro and in vivo.


METHODS
Taxol-resistance (A2780/Taxol, SKOV3/Taxol) ovarian cancer cells and Taxol-sensitive (A2780, SKOV3) ovarian cancer cells were infected with adenovirus vector carrying the CD::UPP gene driven by the MDR1 promoter, followed with 5-fluorocytosine administration. Sensitivity to 5-fluorocytosine (5-FC) was analyzed. The AdMDR1-CD::UPP was subcutaneously injected into the xenografts of the nude mice and 5-FC intraperitoneally. The overall survival and anti-tumor effects were observed.


RESULTS
In vitro, AdMDR1-CD::UPP showed a stronger cytotoxicity in A2780/Taxol cells and SKOV3/Taxol cells than that in A2780 cells and SKOV3 cells. Subcutaneous injection of AdMDR1-CD::UPP into the xenografts of mice bearing tumors of A2780/Taxol cells could significantly suppress the tumor growth and prolong survival as compared with the group of A2780 cells.


CONCLUSIONS
AdMDR1-CD::UPP in combination with 5-FC is an effective approach to suppress the growth of Taxol-resistant ovarian cancer.
Lu
Shi
S
Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Wang
Xiaoyi
X
Xiao
Lan
L
Cai
Liqiong
L
Zhang
Yuan
Y
Wang
Hongbo
H
Wang
Zehua
Z
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics*; D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D045744:Cell Line, Tumor; D043525:Cytosine Deaminase / Q000235:genetics*; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D005260:Female; D005472:Fluorouracil / Q000494:pharmacology; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D051379:Mice; D010051:Ovarian Neoplasms / Q000473:pathology / Q000628:therapy*; D017239:Paclitaxel / Q000494:pharmacology; D010430:Pentosyltransferases / Q000235:genetics*; D011401:Promoter Regions, Genetic; D023041:Xenograft Model Antitumor Assays
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D010430:Pentosyltransferases; C023269:uracil phosphoribosyltransferase; D043525:Cytosine Deaminase; D017239:Paclitaxel; D005472:Fluorouracil