?-catenin signaling inhibitors ICG-001 and C-82 improve fibrosis in preclinical models of endometriosis.

ABSTRACT: Endometriosis exhibits unique characteristics, such as fibrosis, resistance to apoptosis, and promotion of cell proliferation; however, its pathophysiology is not fully understood. Recurrence rates after treatment are high, and the progression risk continues until menopause; hence, more effective therapy for endometriosis is needed. CREB-binding protein (CBP)/?-catenin signaling inhibitors have demonstrated antifibrogenetic effects in liver, lung, and skin diseases. The present study evaluated the effects of two CBP/?-catenin signaling inhibitors, ICG-001 and C-82, on the progression of endometriosis using endometriotic cyst stromal cells from the ovary and normal endometrial stromal cells from the uterus. ICG-001 was also evaluated in a mouse model. ICG-001 and C-82 inhibited cell proliferation, fibrogenesis, and cell migration, and promoted apoptosis in vitro. ICG-001 inhibited the growth of endometriotic lesions in the mouse model. CBP/?-catenin signaling plays an important role in the pathophysiology of endometriosis. Inhibiting the CBP/?-catenin signal can be a therapeutic target for endometriosis.

SUBMITTER: Hirakawa T 

PROVIDER: S-EPMC6934788 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature