Abstract 3233: Lovastatin decreases ovarian cancer cell proliferation and invasion: A case for statin therapy for ovarian cancer patients?

Abstract

Abstract Introduction: Statins are a drug class that inhibit HMG-CoA reductase, the enzyme responsible for converting 3-hydroxy-3-methylglutaryl Co-A into mevalonic acid; the earliest step in cholesterol biosynthesis. Accumulating epidemiologic evidence suggests that cancer patients taking statins for elevated cholesterol respond better to therapy and have longer survival times. In vitro studies have also shown that cancer cells are sensitive to physiologically relevant dosages of statins. Studies have also shown that invasion, proliferation and cell growth are inhibited by statin treatment in several cancer cell lines. Here, we report the effect of lovastatin, a hydrophobic statin, in the inhibition of ovarian cancer cell growth and proliferation, and invasion. Methods: Ovarian cancer cells (ID8, HeyA8, SKOV3ip1, and OVCAR5) were grown to confluency and treated with varying dosages of lovastatin (10, 20, and 40 μM). Morphology was examined using a light microscope. Proliferation was measured using an MTT assay at 24, 48, and 72 hours after treatment in both complete DMEM and serum-free DMEM media. Invasion was measured as the average number of cells that invaded collagen (I)-coated wells using serum free media and lovastatin (20 μM). Histological assessment of HMG-CoA reductase expression was examined in paraffin-embedded human and mouse ovarian tissue. Results: Lovastatin produced a dose-dependent decrease in cell proliferation in HeyA8 and ID8 cancer cell lines. Lovastatin likewise decreased cell proliferation in OVCAR5 and SKOV3ip1 cell lines after 72 hours. Lovastatin inhibited OVCAR5, HeyA8, and SKOV3ip1 cell invasion with exposure to 20 μM concentrations for 24 hours before and during an overnight invasion assay. When HeyA8 cells were exposed to lovastatin during overnight incubation, invasion was also reduced. Histologic assessment of HMG-CoA reductase in human ovarian tumors confirmed expression to the ovarian stroma and to the omentum. Discussion: Our preliminary studies demonstrate the growth inhibitory effects of lovastatin on ovarian cancer cell proliferation and invasion when using dosages that are physiologically relevant. The faster growing types of ovarian cancer cell lines (HeyA8 and ID8) are the most sensitive to lovastatin therapy, while the slower growing ovarian cancer cell lines (OVCAR5 and SKOV3ip1) demonstrate minor effects of lovastatin on cell growth for up to 72 hours. Histologic findings suggests that HMG-CoA is found both in the ovarian stroma and in the omentum of ovarian tumors, indicating that this could be an important target for metastases, as omental metastases are problematic in the management of patients with ovarian tumors. Our next goal is to further determine the molecular mechanisms by which statins inhibit ovarian cancer invasion. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3233. doi:1538-7445.AM2012-3233