U0126 and BAY11-7082 Inhibit the Progression of Endometriosis in a Rat Model by Suppressing the MEK/ERK/NF-κB Pathway.

Abstract

Endometriosis is an aggressive disease. It is the main cause of chronic pelvic pain, dysmenorrhea, and infertility, affecting the well-being of women. This study aimed to explore the role of U0126 and BAY11-7082 in endometriosis (EMs) treatment in rats by targeting the MEK/ERK/NF-κB pathway. The EMs model was generated and the rats were divided into model, dimethyl sulfoxide, U0126, BAY11-708, and control groups (Sham operation group). After 4 weeks of treatment, the rats were sacrificed. Compared with model group, U0126 and BAY11-7082 treatment significantly inhibited ectopic lesion growth, glandular hyperplasia, and interstitial inflammation. Compared to control group, PCNA and MMP9 levels were significantly increased in the eutopic and ectopic endometrial tissues of model group; the levels of MEK/ERK/NF-κB pathway proteins also increased significantly. Compared with model group, MEK, ERK, and NF-κB levels decreased significantly after U0126 treatment and NF-κB protein expression decreased significantly after BAY11-7082 treatment, with no significant difference in MEK and ERK levels. The proliferation and invasion activities of eutopic and ectopic endometrial cells also significantly decreased after U0126 and BAY11-7082 treatment. In summary, our results showed that U0126 and BAY11-7082 inhibited ectopic lesion growth, glandular hyperplasia, and interstitial inflammatory response in EMs rats by inhibiting the MEK/ERK/NF-κB signaling pathway.