Gene therapy of adenovirus mediated CD ::upp/5-FC directed by GSTP1 promoter in cisplatin-resistant ovarian cancer.
OBJECTIVE
To evaluate the specific killing effect of the adenoviral vector in which CD ::upp genes were directed by the GSTP1 promoter on cisplatin-resistant ovarian cancer cells.


METHODS
Cisplatin-sensitive (A2780) and cisplatin-resistant (AD6) ovarian cancer cells were infected with recombinant adenoviral plasmid carrying the CD ::upp gene driven by the GSTP1 promoter and followed with 5-FC administration.


RESULTS
In vitro, when MOI was 100 and 5-FC was 250 microg/ml, relative survival rate of the AD6 cells was only 3.63 +/- 1.01%, while under the same conditions, A2780 cells were 76.50 +/- 2.81%. Significant bystander effect was caused by the CD ::upp gene and 20% of gene-transferred AD6 cells caused death to 80.3% of the total cells. Furthermore, a significant anti-tumor effect of the Ad.GST-CD ::upp/5-FC was observed in nude mice bearing tumors of AD6 cells.


CONCLUSIONS
These results indicated that adenovirus-mediated Ad.GST-CD ::upp/5-FC directed by GSTP1 promoter is an effective approach to overcome cisplatin-resistant ovarian cancer.
Wang
Zehua
Z
Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China. zehuawang@163.net
Cai
Liqiong
L
Wang
Hongbo
H
D000260:Adenoviruses, Human / Q000235:genetics; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D019677:Artificial Gene Fusion; D048708:Cell Growth Processes / Q000187:drug effects; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology*; D043525:Cytosine Deaminase / Q000235:genetics / Q000378:metabolism; D019008:Drug Resistance, Neoplasm; D005260:Female; D005437:Flucytosine / Q000493:pharmacokinetics / Q000627:therapeutic use; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000235:genetics; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D007527:Isoenzymes / Q000235:genetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000628:therapy*; D010430:Pentosyltransferases / Q000235:genetics* / Q000378:metabolism; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
D000970:Antineoplastic Agents; D007527:Isoenzymes; D011993:Recombinant Fusion Proteins; D005437:Flucytosine; D010430:Pentosyltransferases; C023269:uracil phosphoribosyltransferase; C496556:GSTP1 protein, human; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase; C496557:Gstp1 protein, mouse; D043525:Cytosine Deaminase; D002945:Cisplatin