Synthetic Cannabinoid Agonist WIN 55212-2 Targets Proliferation, Angiogenesis, and Apoptosis via MAPK/AKT Signaling in Human Endometriotic Cell Lines and a Murine Model of Endometriosis

合成大麻素激动剂 WIN 55212-2 通过 MAPK/AKT 信号通路靶向人子宫内膜异位症细胞系和子宫内膜异位症小鼠模型中的增殖、血管生成和细胞凋亡

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作者:Harshavardhan Lingegowda ,Jessica E Miller ,Ryan M Marks ,Lindsey K Symons ,Taylor Alward ,Alan E Lomax ,Madhuri Koti ,Chandrakant Tayade

Abstract

Endometriosis (EM) is characterized by the growth of endometrium-like tissue outside the uterus, leading to chronic inflammation and pelvic pain. Lesion proliferation, vascularization, and associated inflammation are the hallmark features of EM lesions. The legalization of recreational cannabinoids has garnered interest in the patient community and is contributing to a greater incidence of self medication; however, it remains unknown if cannabinoids possess marked disease-modifying properties. In this study, we assess the effects of synthetic cannabinoid, WIN 55212-2 (WIN 55), in EM-representative in vitro and in vivo syngeneic mouse models. WIN 55 reduced proliferation and angiogenesis in vitro, via MAPK/Akt-mediated apoptosis. These findings were corroborated in a mouse model of EM, where we found reduced TRPV1 expression in the dorsal root ganglia of the EM mouse model exposed to WIN 55, suggesting reduced signaling of pain stimuli. Ultimately, these pieces of evidence support the use of cannabinoid receptor agonists as a potential therapeutic intervention for EM associated pain and inflammation.

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