In:
Cancer Research, American Association for Cancer Research (AACR), Vol. 71, No. 8_Supplement ( 2011-04-15), p. 3525-3525
Abstract:
Epithelial ovarian cancer (EOC) causes estimated 13,850 deaths in 2010 in the United State. More effective treatment regimens are urgently required for this deadly disease. We and others have obtained ample evidence indicating that lysophosphatidic acid (LPA) plays an important role in EOC development. We have recently shown that the levels of LPA and several other bioactive lipids in the tumor environment of EOC are regulated by Group VIA calcium-independent phospholipase A2 beta (iPLA2β) expressed in tumor microenvironment, suggesting that targeting iPLA2β in both host and tumor cells will likely to be beneficial. To test this idea, we used bromoenol lactone (BEL), a selective inhibitor of iPLA2β in vivo, and found that BEL significantly inhibited EOC tumorigenesis and metastasis in mouse xenograft models using human SKOV3 and HEY ovarian cancer cells. Moreover, the combination of BEL with paclitaxel (PTX), one of the mostly commonly used therapeutics in EOC, almost completely blocked tumor development in the xenograft mouse model. BEL showed very low or 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 combinational effects of BEL and 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 appears to increase the vulnerability of tumor cells to PTX. In summary, this is the first attempt to target iPLA2 using a small inhibitor molecule for cancer treatment in vivo. In addition, the work is also rather unique by targeting activity of the same molecule (iPLA2) in both host and tumor cells. These results provide an important basis for development of new treatment modalities for EOC. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3525. doi:10.1158/1538-7445.AM2011-3525
Type of Medium:
Online Resource
ISSN:
0008-5472
,
1538-7445
DOI:
10.1158/1538-7445.AM2011-3525
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2011
detail.hit.zdb_id:
2036785-5
detail.hit.zdb_id:
1432-1
detail.hit.zdb_id:
410466-3
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