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Cooperative effect of adenoviral p53 gene therapy and standard chemotherapy in ovarian cancer cells independent of the endogenous p53 status

Cancer Gene Therapy volume 11, pages 547–554 (2004)Cite this article

Abstract

Clinical adenoviral p53 gene therapy has been shown by us and others to inhibit tumor growth of ovarian cancer with endogenous mutant p53. This study was designed to test the cooperative antitumor effect of standard combination chemotherapy using paclitaxel and carboplatin together with adenoviral p53 gene transfer in the presence of wild-type and mutant p53. Seven ovarian cancer cell lines with mutant p53 and seven ovarian cancer cell lines with wild-type p53 were tested. An E1-deleted adenovirus type 5 expressing p53 (ACNp53) was used for p53 gene transfer. p53 gene transfer at 50% transduction efficiency significantly reduced IC50 of carboplatin chemotherapy up to 49-fold, of paclitaxel chemotherapy up to six-fold, and of paclitaxel/carboplatin chemotherapy up to 19-fold in the wild-type p53 cell line OV-MZ-5. Synergism between ACNp53 and chemotherapy calculated by median-effect analysis was found at low drug concentrations in all cell lines independent of the p53 mutational status. In conclusion, adenoviral p53 gene transfer significantly increased the sensitivity of ovarian tumor cells to paclitaxel, to carboplatin and/or to the combination of both.

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Acknowledgements

This project was supported by funds of the Deutsche Forschungsgemeinschaft (RU/476/3) granted to IB Runnebaum. We thank S Hees for the technical assistance in sequencing the cDNA of the cell lines confirmed by genomic DNA. Adenoviruses ACNp53 and AdGal was kindly provided by Dr Daniel Maneval (Canji Inc., San Diego, CA).

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Authors and Affiliations

  1. Department of Obstetrics & Gynecology, University of Ulm, Prittwitzstrasse 43, Ulm, D-89075, Germany

    Sven R Quist, Shan Wang-Gohrke, Tanja Köhler, Rolf Kreienberg & Ingo B Runnebaum

  2. Department of Obstetrics and Gynecology, University of Freiburg, Hugstetter Strasse 55, Freiburg, 79106, Germany

    Ingo B Runnebaum

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  1. Sven R Quist
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Quist, S., Wang-Gohrke, S., Köhler, T. et al. Cooperative effect of adenoviral p53 gene therapy and standard chemotherapy in ovarian cancer cells independent of the endogenous p53 status. Cancer Gene Ther 11, 547–554 (2004). https://doi.org/10.1038/sj.cgt.7700727

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