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由雌激素激活的 NLRP3 炎性体可促进人子宫内膜癌的进展
Authors Liu SG, Wu XX, Hua T, Xin XY, Feng DL, Chi SQ, Wang XX, Wang HB
Received 4 June 2019
Accepted for publication 30 July 2019
Published 27 August 2019 Volume 2019:12 Pages 6927—6936
DOI https://doi.org/10.2147/OTT.S218240
Checked for plagiarism Yes
Review by Single-blind
Peer reviewers approved by Dr Shashank Kaushik (PT)
Peer reviewer comments 3
Editor who approved publication: Dr Sanjeev Srivastava
Background: Activation of NLPR3 inflammasome is associated with the development and progression of some types of malignant tumors, but its role in endometrial cancer is unclear. This study aimed to investigate the expression and function of NLRP3 inflammasome in endometrial cancer.
Materials and methods: The expression levels of NLRP3, its inflammasome components and estrogen receptor β in endometrial cancer and paired non-tumor tissues were detected. The effects of NLPR3 silencing or overexpression on the proliferation, migration, and invasion of Ishikawa and HEC-1A cells were determined. The impact of NLPR3 silencing on the growth of implanted tumors was determined in vivo. The effects of estrogen on NLPR3 inflammasome activation and Ishikawa cell proliferation were determined.
Results: The upregulation of NLRP3, ASC, caspase-1, and IL-1β was associated with the progression of endometrial cancer and poor survival. NLPR3 silencing inhibited the proliferation, migration, and invasion of endometrial cancer cells while NLPR3 overexpression had opposite effects. NLPR3 silencing reduced IL-1β and caspase-1 expression and the growth of implanted endometrial tumors, accompanied by decreased pro-IL-1β maturation. Estrogen enhanced NLPR3, ERβ, pro-IL-1β, IL-1β expression, and endometrial cancer cell proliferation, which were mitigated by treatment with ERβ inhibitor but not ERα inhibitor.
Conclusion: Our results suggest that estrogen acts through ERβ to enhance the activation of NLPR3 inflammasome and promote the progression of endometrial cancer. NLPR3 inflammasome may be a new therapeutic target for endometrial cancer.
Keywords: NLRP3, endometrial cancer, estrogen, inflammasome, ERβ