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  • Title: Melatonin Inhibits 17β-Estradiol-Induced Epithelial-Mesenchymal Transition in Endometrial Adenocarcinoma Cells via Upregulating Numb Expression.
    Author: Zhang H, Qi S, Liu Z, Li C, Li M, Zhao X.
    Journal: Gynecol Obstet Invest; 2022; 87(2):89-99. PubMed ID: 35130539.
    Abstract:
    OBJECTIVES: Melatonin (MLT) shows antitumor effects in various tumor types, including endometrial carcinoma. However, the molecular mechanism involved is unclear. In the current study, we investigated the effect of MLT on the estrogen-induced epithelial-mesenchymal transition (EMT) in endometrial adenocarcinoma cells and explored the pathway that might be involved. DESIGN: Laboratory study was via cultured endometrial cancer cells. Design refers only to in vitro experiments. METHODS: In cell culture experiments, cell growth was examined using CCK-8 assays. The expression of Numb and EMT markers in Ishikawa cells was examined using Western blot analysis and real-time PCR. Cell invasion was examined using transwell assays. Cell migration was examined using wound-healing assays and transwell assays. Using immunohistochemistry analysis, the expression of Numb in human endometrial cancers was examined. RESULTS: In immunohistochemistry experiments, we found that 15.2% of atypical endometrial hyperplasia and 15.6% of endometrial carcinoma did not express Numb. In cell culture experiments, MLT inhibited cell proliferation, invasion, and migration induced by 17β-estradiol (E2) in endometrial cancer cells. MLT decreased the expression of vimentin and Slug and increased the expression of Numb and E-cadherin in Ishikawa cells. Numb knockdown in cancer cells significantly increased cell proliferation, invasion, and migration. LIMITATIONS: No animal experiments were performed. CONCLUSIONS: MLT blocked E2-induced cell growth and EMT in endometrial cancer cells via upregulating Numb expression.
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