The effects of STAT3 inhibitors on endometriotic cyst stromal cells

Abstract

Objective: The Signal Transducer and Activator of Transcription 3 (STAT3) protein regulatesmany aspects of cellular functions, such as proliferation, apoptosis, and angiogenesis. Enhanced expression of STAT3 protein has been demonstrated in the endometriotic tissues, suggesting the involvement of this molecule in the pathogenesis of endometriosi.Wedesigned the present study to evaluate the efficacy of STAT3 inhibitors as promising drug for the treatment of endometriosis. Materials and methods: Ovarian endometriotic cyst tissues were obtained from patients who had undergone a salpingooophorectomy or evisceration for the treatment of ovarian endometriotic cysts. This study was approved by the institutional review board of the Faculty of Medicine, Oita University, and written informed consent was obtained from all patients. Ovarian endometriotic cyst stromal cells (ECSCs) were isolated by collagenase digestion and cultured in the presence of STAT3 inhibitors (WP1066, S3I-201, and Cryptotanshinone). The effects of these STAT3 inhibitors on the proliferation, apoptosis, and vascular endothelial growth factor (VEGF) expression were investigated by cell death detection ELISA, caspase3/7 assay, modified MTT assay, and VEGF ELISA, respectively. Results: All of three STAT3 inhibitors inhibited the cell proliferation and VEGF production in ECSCs, and induced the apoptosis of these cells. Discussion: STAT3 inhibitors are promising candidates for the treatment of endometriosis. At present, STAT3 inhibitors are clinically used as the anti-cancer drugs. The clinical application of these agents for endometriosis is expected in the future.