NLRP3 inflammasome activation by estrogen promotes the progression of human endometrial cancer.

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 beta 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-1 beta 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-1 beta and caspase-1 expression and the growth of implanted endometrial tumors, accompanied by decreased pro-IL-1 beta maturation. Estrogen enhanced NLPR3, ER beta, pro-IL-1 beta, IL-1 beta expression, and endometrial cancer cell proliferation, which were mitigated by treatment with ER beta inhibitor but not ER alpha inhibitor. Conclusion: Our results suggest that estrogen acts through ER beta 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.