Inhibition of the mevalonate pathway augments the activity of pitavastatin against ovarian cancer cells.

摘要: Only 40% of patients with advanced ovarian cancer survive more than 5 years. We have previously shown that pitavastatin induces regression xenografts in mice. To evaluate whether the response cells to is potentiated by farnesyl diphosphate synthase inhibitors or geranylgeraniol transferase I inhibitors, we evaluated combinations zoledronic acid, risedronate and GGTI-2133 a panel cells. Pitavastatin (IC50 = 0.6–14 μM), acid (IC50 = 21–57 μM), (IC50 > 100 μM) (IC50 > 25 μM) inhibited growth cell cultures. Combinations displayed additive synergistic effects assays in 10 11 lines as well trypan blue exclusion, cellular ATP caspase 3/7, 8 9 assays. reduced levels GGT-IIβ membrane localization several small GTPases this was acid. siRNA GGT-Iβ used combination, but not when individually, significantly increased sensitivity pitavastatin. These data suggest drug already clinical use, may be usefully combined treatment cancer.