Combination therapy of an inhibitor of group VIA phospholipase A 2 with paclitaxel is highly effective in blocking ovarian cancer development

Hui Li, Zhenwen Zhao, Caryl Antalis, Zhanzhong Zhao, Robert Emerson, Gang Wei, Sheng Zhang, Zhong Yin Zhang, Yan Xu

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Abstract

We and others have shown that calcium-independent phospholipase A 2 (iPLA2) is involved in epithelial ovarian cancer (EOC). Hence, we propose that iPLA2 is a potential effective and novel target for EOC. We tested this concept and found that bromoenol lactone (BEL), a selective inhibitor of iPLA2, significantly inhibited EOC metastatic tumor growth in mouse xenograft models using human SKOV3 and HEY ovarian cancer cells. Moreover, the combination of BEL with paclitaxel (PTX), one of the most commonly used therapeutic agents in EOC, almost completely blocked tumor development in the xenograft mouse model. BEL showed no detectable cytotoxic effects in mice. Another iPLA2 inhibitor, FKGK11, also inhibited tumor development in the xenograft mouse model, supporting that the major target of action was iPLA2. The additional effects of BEL with PTX in vivo likely stem from their distinct cellular effects. BEL and FKGK11 reduced adhesion, migration, and invasion of EOC cells in vitro; the reduced ability to adhere, migrate, and invade seems to increase the vulnerability of tumor cells to PTX. These results provide an important basis for the development of new treatment modalities for EOC.

Original languageEnglish (US)
Pages (from-to)452-461
Number of pages10
JournalAmerican Journal of Pathology
Volume179
Issue number1
DOIs
StatePublished - Jul 1 2011

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ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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