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

doi:10.1002/jcp.26156

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Title:	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
Authors:	Chen, Ming-Jenn Cheng, An-Ching Lee, Ming-Fen Hsu, Yi-Chiang
Contributors:	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
Keywords:	colorectal cancer cyclin D1 G(1) arrest glycogen synthase kinase 3 simvastatin
Date:	2018-06
Issue Date:	2019-11-15 15:48:40 (UTC+8)
Publisher:	WILEY
Abstract:	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.
???metadata.dc.relation.uri???:	http://dx.doi.org/10.1002/jcp.26156
Relation:	Journal of Cellular Physiology, v.233, n.6, pp.4618-4625
Appears in Collections:	[Dept. of Sports Management] Periodical Articles

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