目的 研究米非司酮在子宮內(nèi)膜癌中的功能和潛在分子機制。方法 通過細胞增殖實驗研究不同質(zhì)量濃度（10、50、100 μg/mL）米非司酮以及隨著時間變化米非司酮對子宮內(nèi)膜癌細胞的影響；蛋白免疫印記實驗及免疫熒光實驗研究米非司酮（50 μg/mL）對子宮內(nèi)膜癌細胞內(nèi)外泌體分泌、外泌體調(diào)控關(guān)鍵蛋白的表達、外泌體關(guān)鍵調(diào)控蛋白對外泌體分泌的影響。結(jié)果 隨著加入子宮內(nèi)膜癌細胞內(nèi)的米非司酮質(zhì)量濃度升高和時間推移，子宮內(nèi)膜癌細胞增殖速率顯著減慢，同時細胞狀態(tài)變差，數(shù)目顯著減少；米非司酮顯著降低外泌體蛋白胞外分泌，包括外泌體總蛋白以及標志蛋白CD63和Gp96等，使其滯留在胞內(nèi)；米非司酮顯著降低外泌體分泌調(diào)控蛋白Rab27a和Rab27b的表達；敲低外泌體分泌調(diào)控蛋白Rab27a和Rab27b的表達顯著降低外泌體總蛋白以及標志蛋白CD63的胞外分泌。結(jié)論 米非司酮通過抑制外泌體分泌調(diào)控蛋白Rab27a和Rab27b的表達，從而抑制外泌體分泌，最終導(dǎo)致子宮內(nèi)膜癌細胞增殖顯著減慢。

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

河南省重點科技計劃項目（2019BJ0366）