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    题名: Depsipeptide (FK228) inhibits growth of human prostate cancer cells
    作者: Lai, MT (Lai, Ming-Tsung);Yang, CC (Yang, Chuan-Ching);Lin, TY (Lin, Tsai-Yun);Tsai, FJ (Tsai, Fuu-Jen);Chen, WC (Chen, Wen-Chi)
    贡献者: Department of Biotechnology
    关键词: FK228;histone deacetylase inhibitor;prostate-specific antigen;prodrug;lung metastasis;prostate adenocarcinoma;HISTONE DEACETYLASE INHIBITORS;PHASE-II;TRIAL;ACID
    日期: 2008-03
    上传时间: 2010-03-26 02:30:00 (UTC+0)
    出版者: Asia University
    摘要: FK228 (depsipeptide) is a natural prodrug that inhibits class I histone deacetylases. We aimed to investigate the effects FK228 has on prostate cancer cells in vivo. In non-obese diabetic-severe combined immunodeficient mice implanted with human prostate cancer cells, 50 mg/kg FK228 given orally 3 times a week inhibited tumor growth and metastasis. The median time to the experimental end point (tumor volume 2 cm 3 or death) in the untreated group was 52 days, and average tumor volume was 0.8 +/- 0.18 cm(3). At the same time, 94.4% of FK228-treated mice survived and had average tumor volumes of 0.37 +/- 0.1 cm(3). All untreated animals died at 98 days, whereas, 61% of treated animal remained alive. Sizeable metastatic tumors positively stained for prostate-specific antigen (PSA), and limited air gaps were found in the lungs of untreated mice. In animals treated with FK228, lung morphology appeared normal. Primary tumors of treated animals were highly positive for PSA, and had an increased level of p21 and the proapoptotic protein Bax. Sections taken from FK228-treated animals and examined under an electron microscope showed condensed chromatin and apoptotic bodies. PSA serum levels were higher in untreated than in treated animals and correlated with tumor volume. Because prolonged oral administration of 50 mg/kg or a single oral dose of 1.2 g/kg FK228 did not cause adverse effects and inhibited proliferation of human prostate cancer cells in vivo, FK228 likely has a potential anticancer effect for prostate cancer. (c) 2008 Elsevier Inc. All rights reserved.
    關聯: UROLOGIC ONCOLOGY-SEMINARS AND ORIGINAL INVESTIGATIONS, 26 (2): 182-189
    显示于类别:[生物科技學系] 期刊論文

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