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AIM: To investigate the effects of 17β-estradiol via estrogen receptors(ER) or direct administration of ER agonists on human colorectal cancer. METHODS: Lo Vo 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, Lo Vo 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 Lo Vo 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 Lo Vo 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 17β-estradiol and/or ER agonists in human Lo Vo 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 17β-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 17β-estradiol and/or ER agonists downregulate migration-related proteins through the p53 signaling pathway in human Lo Vo colorectal cancer cells. These findings suggest that p53 plays a critical role in the 17β-estradiol and/or ER agonist-mediated protective activity against colorectal cancer progression. In addition, 17β-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 Lo Vo 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 Lo Vo cells. That E2 and/or ER agonists may impair Lo Vo 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.