Lycorine hydrochloride selectively inhibits human ovarian cancer cell proliferation and tumor neovascularization with very low toxicity
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文摘
Uncontrolled tumor cell proliferation and robust neovascularization are prominent features of aggressive ovarian cancers. Although great efforts in anti-ovarian cancer therapy have been made in the past 4 decades, the 5-year survival rates for ovarian cancer patients are still poor, and effective drugs to cure ovarian cancer patients are absent. In this study, we evaluated the anti-cancer effects of lycorine hydrochloride (LH), a novel anti-ovarian cancer agent, using the highly-invasive ovarian cancer cell line, Hey1B, as a model. Our data showed that LH effectively inhibited mitotic proliferation of Hey1B cells (half maximal inhibitory concentration = 1.2 ¦ÌM) with very low toxicity, resulting in cell cycle arrest at the G2/M transition through enhanced expression of the cell cycle inhibitor p21 and marked down-regulation of cyclin D3 expression. Moreover, LH suppressed both the formation of capillary-like tubes by Hey1B cells cultured in vitro and the ovarian cancer cell-dominant neovascularization in vivo when administered to Hey1B-xenotransplanted mice. LH also suppressed the expression of several key angiogenic genes, including VE-cadherin, vascular endothelial growth factor, and Sema4D, and reduced Akt phosphorylation in Hey1B cells. These results suggest that LH selectively inhibits ovarian cancer cell proliferation and neovascularization and is a potential drug candidate for anti-ovarian cancer therapy.

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