Estradiol agonists inhibit human LoVo colorectal-cancer cell proliferation and migration through p53

doi:10.3748/wjg.v20.i44.16665

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標題:	Estradiol agonists inhibit human LoVo colorectal-cancer cell proliferation and migration through p53
作者:	Hsu, Hsi-Hsien Kuo, Wei-Wen Ju, Da-Tong Yeh, Yu-Lan Tu, Chuan-Chou Tsai, Ying-Lan Shen, Chia-Yao Chang, Sheng-Huang Chung, Li-Chin Huang, Chih-Yang
貢獻者:	醫務管理系
關鍵字:	Estrogen Estrogen agonist Estrogen receptors Human colon cancer cell p53
日期:	2014-11
上傳時間:	2015-05-06 21:20:57 (UTC+8)
出版者:	Baishideng Publishing Group Inc
摘要:	AIM: To investigate the effects of 17 beta-estradiol via estrogen receptors (ER) or direct administration of ER agonists on human colorectal cancer. METHODS: LoVo cells were established from the Bioresource Collection and Research Center and cultured in phenol red-free DMEM (Sigma, United States). To investigate the effects of E2 and/or ER selective agonists on cellular proliferation, LoVo colorectal cells were treated with E2 or ER-selective agonists for 24 h and 48 h and subjected to the MTT (Sigma) assay to find the concentration. And investigate the effects of E2 and/or ER selective agonists on cell used western immunoblotting to find out the diversification of signaling pathways. In order to observe motility and migration the wound healing assay and a transwell chamber (Neuro Probe) plate were tased. For a quantitative measure, we counted the number of migrating cells to the wound area post-wounding for 24 h. We further examined the cellular migration-regulating factors urokinase-type plasminogen activator (u-PA), tissue-type plasminogen activator (t-PA) and matrix metalloproteinase (MMP)-9 in human LoVo cells so gelatin zymography that we used and gelatinolytic activity was visualized by Coomassie blue staining. And these results are presented as means +/- SE, and statistical comparisons were made using Student's t-test. RESULTS: The structure was first compared with E2 and ER agonists. We then treated the LoVo cells with E2 and ER agonists (10-8 mol/L) for 24 h and 48 h and subsequently measured the cell viability using MTT assay. Our results showed that treatment with 17 beta-estradiol and/or ER agonists in human LoVo colorectal cancer cells activated p53 and then up-regulated p21 and p27 protein levels, subsequently inhibiting the downstream target gene, cyclin D1, which regulates cell proliferation. Taken together, our findings demonstrate the anti-tumorigenesis effects of 17 beta-estradiol and/or ER agonists and suggest that these compounds may prove to be a potential alternative therapy in the treatment of human colorectal cancer. These results demonstrate that 17 beta-estradiol and/or ER agonists downregulate migration-related proteins through the p53 signaling pathway in human LoVo colorectal cancer cells. These findings suggest that p53 plays a critical role in the 17 beta-estradiol and/or ER agonist-mediated protective activity against colorectal cancer progression. In addition, 17 beta-estradiol and/or ER agonists dramatically inhibited cell migration and reduced the expression of u-PA, t-PA and MMP-9 as well as MMP-2/9 activity in LoVo cells, which regulate cell metastasis. Moreover, we observed that pretreatment with a p53 inhibitor significantly blocked the anti-migration effects of E2 and/or ER agonists on LoVo cells. That E2 and/or ER agonists may impair LoVo cell migration by modulating migration-related factors via the p53 tumor suppressor gene. CONCLUSION: Direct ER treatment may prove to be an attractive alternative therapy in the treatment of human colorectal tumors in the future. (C) 2014 Baishideng Publishing Group Inc. All rights reserved.
關聯:	World Journal of Gastroenterology, v.20 n.44, pp.16665-16673
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