The mTOR/AKT Inhibitor Temsirolimus Prevents Deep Infiltrating Endometriosis in Mice

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AI-generated summary by claude@2026-06, 2026-06-08

Temsirolimus, an mTOR/AKT inhibitor, reduced the size and number of deep infiltrating endometriosis lesions in a mouse model.

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Abstract

Deep infiltrating endometriosis (DIE) is a particular clinical and histological entity of endometriosis responsible for chronic pelvic pain and infertility. Here we characterize the proliferative phenotype of DIE cells, to explore the cellular and molecular mechanisms that could explain their aggressive potential. In addition, the inhibition of mTOR/AKT pathway was tested, as a potential treatment of DIE. Included were 22 patients with DIE and 12 control patients without endometriosis. Epithelial and stromal cells were extracted from biopsies of eutopic endometrium and deep infiltrating endometriotic nodules from patients with DIE. Cell proliferation was determined by thymidine incorporation. Oxidative stress was assayed by spectrofluorometry. The ERK and mTOR/AKT pathways were analyzed in vitro by Western blot and for AKT in vivo in a mouse model of DIE. The proliferation rate of eutopic endometrial cells and of deep infiltrating endometriotic cells from DIE patients was higher than that of endometrial cells from controls. The hyperproliferative phenotype of endometriotic cells was associated with an increase in endogenous oxidative stress, and with activation of the ERK and mTOR/AKT pathways. mTOR/AKT inhibition by temsirolimus decreased endometriotic cell proliferation both in vitro and in vivo in a mouse model of DIE. Blocking the mTOR/AKT pathway offers new prospects for the treatment of DIE.

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Condition tags

endometriosisdie_deep_infiltrating

MeSH descriptors

Endometriosis Sirolimus Adult Animals Biopsy Cell Proliferation Disease Models, Animal Endometriosis Endometrium Endometrium Female Humans Mice Mice, Nude Middle Aged Oxidative Stress Phenotype Protein Kinase Inhibitors Protein Kinase Inhibitors Reactive Oxygen Species

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europepmc
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