目的 研究米非司酮在子宫内膜癌中的功能和潜在分子机制。方法 通过细胞增殖实验研究不同质量浓度（10、50、100 μg/mL）米非司酮以及随着时间变化米非司酮对子宫内膜癌细胞的影响；蛋白免疫印记实验及免疫荧光实验研究米非司酮（50 μg/mL）对子宫内膜癌细胞内外泌体分泌、外泌体调控关键蛋白的表达、外泌体关键调控蛋白对外泌体分泌的影响。结果 随着加入子宫内膜癌细胞内的米非司酮质量浓度升高和时间推移，子宫内膜癌细胞增殖速率显著减慢，同时细胞状态变差，数目显著减少；米非司酮显著降低外泌体蛋白胞外分泌，包括外泌体总蛋白以及标志蛋白CD63和Gp96等，使其滞留在胞内；米非司酮显著降低外泌体分泌调控蛋白Rab27a和Rab27b的表达；敲低外泌体分泌调控蛋白Rab27a和Rab27b的表达显著降低外泌体总蛋白以及标志蛋白CD63的胞外分泌。结论 米非司酮通过抑制外泌体分泌调控蛋白Rab27a和Rab27b的表达，从而抑制外泌体分泌，最终导致子宫内膜癌细胞增殖显著减慢。

Objective To study the function and potential molecular mechanism of mifepristone on endometrial cancer. Methods Cell proliferation experiments was used to study the effects of different concentrations of mifepristone on endometrial cancer cells, and the effects of mifepristone on endometrial cancer cells over time. Western blotting and immunofluorescence experiments were used to study the effects of mifepristone on exocrine secretion, expression of key exosome regulatory proteins, and key exosome regulatory proteins on exosome secretion of endometrial cancer cells. Results With the increase of mifepristone concentration in the endometrial cancer cells and the passage of time, the proliferation rate of the endometrial cancer cells significantly slowed down, and at the same time, the state of the cells deteriorated, and the number decreased significantly. Mifepristone could significantly reduce the extracellular secretion of exosomal proteins, including total exosome proteins and marker proteins CD63 and Gp96, so that it remained in the cell. Mifepristone could significantly reduce the exosome secretion regulatory proteins Rab27a and Rab27b expression. The extracellular secretion of total exosomal protein and marker protein CD63 reduced significantly by knocking down the expression of exosome secretion regulatory proteins Rab27a and Rab27b. Conclusion Mifepristone can inhibit the expression of exosome secretory regulatory proteins Rab27a and Rab27b, thereby inhibiting exosome secretion, which ultimately leads to a significant slowdown of endometrial cancer cell proliferation.

R984

河南省重点科技计划项目（2019BJ0366）