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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. [ABSTRACT FROM AUTHOR]

Background: Sperm-associated antigen 9 (SPAG9), a recently characterized oncogene, may serve as a marker for the early diagnosis of endometrial cancer. However, whether SPAG9 can be a prognostic marker of complex atypical endometrial hyperplasia (CAEH) or grade 1 endometrioid adenocarcinoma (EA) treated with progestin is still unknown.Methods: Progestin therapy was performed in 27 women diagnosed with CAEH (19/27, CAEH group) or grade 1 EA (8/27, EA group). The expression of SPAG9 was measured in pre and post progestin-treated endometrial specimens by immunohistochemistry. The expression of SPAG9 was also examined by real-time polymerase chain reaction (PCR) and Western blot in Ishikawa cells and ECC-1 cells with or without progestin treatment.Results: (1) CAEH showed a significantly better therapeutic efficacy than EA. (2) The expression of SPAG9 was lower in CAEH than in EA. (3) SPAG9 expression significantly declined in the endometrial tissues of women responding to progestin. (4) Significant downregulations of SPAG9 were validated by reverse transcription PCR (RT-PCR) and Western blot both in Ishikawa cells and ECC-1 cells treated with progestin.Conclusion: SPAG9 may be associated with the efficacy of progestin treatment in CAEH and grade 1 EA. It may help to distinguish CAEH from grade 1 EA and serve as a new prognostic marker of CAEH or grade 1 EA treated with progestin. [ABSTRACT FROM AUTHOR]