Progesterone receptor antagonist provides palliative effects for uterine leiomyoma through a Bcl-2/Beclin1-dependent mechanism

Abstract

Uterine leiomyoma is the most common benign smooth muscle tumor of uterus in women of reproductive age, with a high lifetime incidence. Nowadays, the exploration on the pharmacotherapies, such as progesterone receptor antagonist (PRA) requires more attention. Hence, the current study aimed to examine whether mifepristone, a PRA, influences the autophagy and apoptosis of uterine leiomyoma cells. Primary uterine leiomyoma cells were collected from 36 patients diagnosed with uterine leiomyoma to establish PR-M-positive (PR-M[+]) cells. The lentiviral vector overexpressing or silencing PR-M was subsequently delivered into one part of PR-M(+) cells in order to evaluate the role of PR-M in PR-M(+) cells. The results obtained revealed that cell viability was increased, while cell autophagy and apoptosis were diminished in the PR-M(+) cells treated with overexpressed PR-M, whereby the Bcl-2 level was elevated and the level of Beclin1 was reduced. An opposite trends were identified following treatment with knockdown of PR-M. Mifepristone at different concentrations (low, moderate, or high) was then applied to treat another part of the PR-M(+) cells. Mifepristone was identified to promote cell autophagy and apoptosis, decrease Bcl-2 level and increase Beclin1 level, accompanied by weakened interaction between Bcl-2 and Be-clin1. Moreover, these effects of mifepristone on PR-M(+) cells were enhanced with increasing of the concentration. Taken together, the present study present evidence indicates the ability of PRA to regulate the Bcl-2/Beclin1 axis, ultimately promoting the autophagy and apoptosis of uterine leiomyoma cells, highlighting that PRA serves as a promising therapeutic target for the treatment of uterine leiomyoma.