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)/β-catenin signaling inhibitors have demonstrated antifibrogenetic effects in liver, lung, and skin diseases. The present study evaluated the effects of two CBP/β-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/β-catenin signaling plays an important role in the pathophysiology of endometriosis. Inhibiting the CBP/β-catenin signal can be a therapeutic target for endometriosis.
Highlights
Endometriosis is a benign estrogen-dependent disease in which endometrial tissue develops outside the uterus, such as in the ovaries, peritoneum, and rectovaginal space
An endometrial gland and endometrial stromal cells are shown. (B) hematoxylin and eosin (HE) staining of endometriosis. (C) A representative image of immunohistochemical staining of a normal endometrium with anti-human β-catenin. (D) A representative image of immunohistochemical staining of endometriosis with anti-human β-catenin. (E,F) Significant upregulation of β-catenin protein expression in endometriotic cyst stromal cells (ECSC) compared with normal endometrial stromal cells (NESC) is shown by western blotting. n = 5, *p < 0.01, Student’s t-test
The Wnt/β-catenin signaling pathway is further involved in progression of diseases by regulating cell proliferation, migration, invasion, and fibrogenesis[11,12,16,17]
Summary
Endometriosis is a benign estrogen-dependent disease in which endometrial tissue develops outside the uterus, such as in the ovaries, peritoneum, and rectovaginal space. Pain from endometriosis can be treated by excising the peritoneal lesions and ovarian cysts, or using hormonal agents such as progestin, oral contraceptives, and gonadotropin-releasing hormone agonists. These treatment strategies are associated with high recurrence rates[1]; more effective therapy is needed. The epithelial cells of both the normal endometrium (Fig. 1C) and endometriotic cyst (Fig. 1D) were stained almost and intensely with β-catenin. The stromal cells were stained partially and weakly, western blot analysis showed that β-catenin expression in ECSC was significantly higher than in NESC (Fig. 1E,F, Student’s t-test, p = 0.0020)
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