Abstract
Abstract Eicosanoid-related enzymes may be implicated in the pathogenesis of ovarian cancer. We found that high grade serous ovarian carcinoma had a significantly higher level of 12-LOX expression than normal ovarian epithelium. These data led us to hypothesize that the lipoxygenase pathway is important in the regulation of ovarian cancer growth. In the present study, we examined the role of 12-lipoxygenase (12-LOX), the main human 12-HETE generating enzyme, in the regulation of proliferation and survival in epithelial ovarian cancer in vitro and ovarian cancer development and angiogenesis in vivo. Down-regulation of the 12-LOX expression using 12-LOX siRNA also resulted in markedly reduction in the epithelial ovarian cancer (EOC) OVCAR-3 growth as we have previously observed with BMD-122, a selective 12-LOX inhibitor. In addition, BMD-122 significant inhibited the VEGF expression whereas purified 12-HETE increase VEGF expression in OVCAR-3 cells. Furthermore, we found that BMD-122 markedly decreases angiogenesis induced by OVCAR-3 in a Matrigel plug angiogenesis assay. Systemic administration of BMD-122 to nude mice bearing experimentally-induced ovarian cancer resulted in a 60 % decrease in tumor size. These data suggest that 12-LOX may be involved in regulation of ovarian cancer growth, survival and cancer-induced angiogenesis. Thus inhibition of 12-LOX could be useful as adjuvant therapy of ovarian cancer. 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 4467. doi:10.1158/1538-7445.AM2011-4467
Published Version
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