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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 |
| 顯示於類別: | [醫務管理系(所)] 期刊論文
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