
Vol. 54, No. 1, 2008
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Experimental Chemotherapy
Role of Triptolide as an Adjunct Chemotherapy for Ovarian Cancer
Suzanne D. Westfall, Eric E. Nilsson, Michael K. Skinner
Center for Reproductive Biology, School of Molecular Biosciences, Washington State University, Pullman, Wash., USA
Address of Corresponding Author
Chemotherapy 2008;54:67-76 (DOI: 10.1159/000112419)
Key Words
- Ovarian cancer
- Triptolide
- Carboplatin
- Phosphatidylinositol 3-kinase inhibitor
- LY294002
Abstract
Background: Triptolide (TPL) has been identified as the active component of the Tripterygium wilfordii hook F plant and demonstrated to possess antitumor properties and induce apoptosis in a variety of tumor cell lines. Since TPL actions are associated with changes in the activities of both p53 and NF B, which are implicated in the chemoresistance of ovarian cancer, the ability of TPL to be a potential chemotherapeutic for ovarian cancer was considered. Methods: TPL actions on human ovarian cancer cells were investigated in vitro and in vivo with a nude mouse model to monitor tumor burden both in the absence or presence of other chemotherapy agents. Results: TPL was effective as a single agent in inducing apoptosis of ovarian cancer cells in vitro, but not in vivo. TPL enhanced the cytotoxicity of carboplatin in culture and enhanced carboplatin-mediated reduction of tumor burden in nude mice inoculated with human ovarian cancer cells. Previously, a phosphatidylinositol 3-kinase (PI3 kinase) inhibitor was found to enhance carboplatin actions on ovarian cancer. Interestingly, the combined treatment of TPL, PI3 kinase inhibitor LY294002 and carboplatin was found to dramatically reduce ovarian tumor progression and burden in nude mice. Conclusion: In 44% of the animals tested the combined treatment caused complete regression of ovarian cancer. Combined observations indicate TPL may be an effective adjunct chemotherapy for ovarian cancer. Copyright © 2007 S. Karger AG, Basel
Author Contacts Michael K. Skinner Center for Reproductive Biology, School of Molecular Biosciences Washington State University Pullman, WA 99164-4231 (USA) Tel. +1 509 335 1524, Fax +1 509 335 2176, E-Mail skinner@mail.wsu.edu
Article Information
Received: June 9, 2006
Accepted after revision: June 4, 2007
Published online: December 10, 2007
Number of Print Pages : 10
Number of Figures : 9, Number of Tables : 0, Number of References : 38 |
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