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    標題: Simvastatin induces G(1) arrest by up-regulating GSK3 and down-regulating CDK4/cyclin D1 and CDK2/cyclin E1 in human primary colorectal cancer cells
    作者: Chen, Ming-Jenn
    Cheng, An-Ching
    Lee, Ming-Fen
    Hsu, Yi-Chiang
    貢獻者: Chi Mei Med Ctr, Dept Surg
    Chia Nan Univ Pharm & Sci, Dept Sports Management, Coll Leisure & Recreat Management
    Chang Jung Christian Univ, Dept Nutr & Hlth Sci, 1 Changda Rd Gueiren Dist
    Chang Jung Christian Univ, Dept Med Sci Ind, Coll Hlth Sci, 1 Changda Rd Gueiren Dist
    關鍵字: colorectal cancer
    cyclin D1
    G(1) arrest
    glycogen synthase kinase 3
    simvastatin
    日期: 2018-06
    上傳時間: 2019-11-15 15:48:40 (UTC+8)
    出版者: WILEY
    摘要: Simvastatin (SIM), a widely used cholesterol-lowering drug, also exhibits tumor-suppressive potentials in several types of malignancy. Colorectal cancer (CRC), the third most common malignant neoplasm, accounts for the second most leading cause of cancer-related deaths worldwide. In the present study, we investigated the anticancer effects of SIM on CRC using primary cancer cells lines (CPs: CP1 to CP5) isolated from five Taiwanese colorectal cancer patients as a model for colorectal cancer. We treated all five CPs with SIM for 24-72hr and observed the respective cell viability by an MTT assay. SIM increased DNA content of the G(1) phase, but did not induce apoptosis/necrosis in CPs as shown by flow cytometry with propidium iodide (PI)/annexin V double staining and PI staining. The expression of G(1) phase-related proteins was analyzed by RT-PCR and Western blotting. SIM suppressed cell growth and induced cell cycle G(1)-arrest by suppressing the expression of CDK4/cyclin D1 and CDK2/cyclin E1, but elevating the expression of glycogen synthase kinase 3 in CPs. Our findings indicate that SIM may have antitumor activity in established colorectal cancer.
    link: http://dx.doi.org/10.1002/jcp.26156
    關聯: Journal of Cellular Physiology, v.233, n.6, pp.4618-4625
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