Chia Nan University of Pharmacy & Science Institutional Repository:Item 310902800/24227
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    標題: CHM-1 Induces Apoptosis via p38-Mediated Up-regulation of DR5 Expression in Human Ovarian Cancer SKCOV3 Cells
    作者: Jang-Chang Lee (李正常)
    Li-Chen Chou (周立琛)
    Li-Jiau Huang (黃麗嬌)
    Tzong-Der Wayd (魏宗德)
    Sheng-Chu Kuo (郭盛助)
    日期: 2011
    上傳時間: 2011-06-23 14:57:18 (UTC+8)
    摘要: Ovarian cancer is a leading cause of death due to neoplasm of the female genital tract. Treatment for advanced-stage disease remains limited, and an effective drug for ovarian cancer is urgently needed today. In the present study, MTT assay was used to evaluate the anti-proliferative effect of the 2-phenyl quinolone derivatives for developing new anti-ovarian cancer drugs. CHM-1 was the most active compound, and it exhibited potent anti-proliferative activity against human ovarian cancer cells. CHM-1 inhibited the growth of SKOV3 cells and induced apoptosis in a concentration-dependent manner, but it was less cytotoxicity to human diploid skin fibroblast Detroit 551 cells. The western blot experiments showed that CHM-1 caused the up-regulation of death receptor (DR) 5 and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). Interestingly, CHM-1-mediated cellular apoptosis was found to be closely involved with the p38-mediated up-regulation of DR5 expression. In an SKOV3 subcutaneous xenograft model, both CHM-1 and its phosphate, CHM-l-P caused significant dose- and time-dependent tumor regression. Furthermore, CHM-1 inhibited tumor growth and prolonged the lifespan in the SKOV3 ip1/luc orthotopic xenograft model. Intravenous administration of CHM-l-P significantly prolonged the survival time in the SKOV3/ICR-Foxn1nu orthotopic xenograft model. Based on their excellent antitumor activity with interesting mechanism of action, CHM-1 and CHM-1-P were considered new anti-ovarian cancer drug candidates.
    關聯: 2011年台俄有機、藥物與生物化學交流暨藥物化學研討會，起迄日：2011/04/06~2011/04/05，地點：溪頭台大實驗林
    显示于类别:[藥理學院] 2011年台俄有機、藥物與生物化學交流暨藥物化學研討會

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