Growth suppression of human ovarian carcinoma OV-MZ-2a and OV-MZ-32 cells mediated by gene transfer of wild-type p53 enhanced by chemotherapy in vitro.
OBJECTIVE
The aim of this work was to observe the growth and chemosensitivity of human ovarian cancer OV-MZ-2a and OV-MZ-32 cells following adenovirus-based wild-type p53 (Ad-p53) gene transfer alone or combined with chemotherapeutic agents.


METHODS
Transduction efficiency was determined with a reporter construct of adenovirus galactosidase by staining with 5-bromo-4-chloro-3-indolyl beta-D-galactoside. For growth inhibition, OV-MZ-2a or OV-MZ-32 cells were infected with Ad-p53 particles at a multiplicity of infection (m.o.i.) of 0.2-20, alone or combined with the chemotherapeutic agents taxol, cisplatin, doxorubicin or mitomycin C. Growth inhibition (assayed by trypan blue exclusion), target gene expression (by Western blotting) and clonogenicity (by soft-agar assay) were determined following Ad-p53 transfer.


RESULTS
High transduction efficiency was observed following adenovirus galactosidase gene transfer; 94% of OV-MZ-2a cells and 69% of OV-MZ-32 cells expressed the transgene. Following transfer of Ad-p53 into the two cell lines, a high level of p53 expression was detected after 12, 24, 48, 72 and 96 h in OV-MZ-2a cells. At a m.o.i of 20, 96% and 90% growth inhibition were achieved in OV-MZ-2a cells and OV-MZ-32 cells respectively. Clonogenicity was lost completely in both cell lines following wild-type p53 transfer. Meanwhile, Ad-p53 gene transfer combined with taxol, cisplatin, doxorubicin or mitomycin C was shown to be even more effective in suppressing growth in the two cell lines.


CONCLUSIONS
Our results may suggest that wild-type p53 gene transfer mediated by an adenoviral vector is a potential strategy for treating ovarian cancer, and a combination of Ad-p53 gene transfer and chemotherapeutic agents may be an even better treatment of the cancer.
Wu
Q
Q
Department of Urology, University of Ulm, Germany. qiwu@acsu.buffalo.edu
Kreienberg
R
R
Runnebaum
I B
IB
D000230:Adenocarcinoma / Q000188:drug therapy / Q000235:genetics* / Q000628:therapy*; D000256:Adenoviridae; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D015153:Blotting, Western; D002945:Cisplatin / Q000627:therapeutic use; D004317:Doxorubicin / Q000627:therapeutic use; D005260:Female; D017353:Gene Deletion; D015972:Gene Expression Regulation, Neoplastic; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D006801:Humans; D016685:Mitomycin / Q000627:therapeutic use; D020125:Mutation, Missense; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000628:therapy*; D017239:Paclitaxel / Q000008:administration & dosage; D014161:Transduction, Genetic; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*; D015854:Up-Regulation
D016159:Tumor Suppressor Protein p53; D016685:Mitomycin; D004317:Doxorubicin; D017239:Paclitaxel; D002945:Cisplatin