标题：Association of expression of XIAP-associated factor 1 (XAF1) with clinicopathologic factors, overall survival, microvessel density and cisplatin-resistance in ovarian cancer
作者：Wang, YunXia; Mao, HongLuan; Hao, QingZhi; Wang, Yu; Yang, YongMei; Shen, Liang; Huang, ShanYing; Liu, PeiShu
作者机构：[Wang, YunXia; Mao, HongLuan; Wang, Yu; Shen, Liang; Liu, PeiShu] Shandong Univ, Qilu Hosp, Dept Obstet & Gynecol, Jinan 250012, Shandong, Peoples R C 更多
通讯作者地址：[Liu, PS]Shandong Univ, Qilu Hosp, Dept Obstet & Gynecol, Wenhua Xi Rd 107, Jinan 250012, Shandong, Peoples R China.
关键词：X-linked inhibitor of apoptosis; XIAP-associated factor 1; Epithelial; ovarian cancer; Microvessel density; Cisplatin; Chemosensitivity
摘要：XIAP-associated factor 1 (XAF1) was identified as a novel X-linked inhibitor of apoptosis (XIAP) binding partner that can reverse the anti-apoptotic effect of XIAP. XAF1 levels are greatly decreased in many cancer tissues and cell lines. The aim of this study was to investigate the expression of XAF1 and XIAP in advanced epithelial ovarian cancer and role of XAF1 in cisplatin resistance of ovarian cancer cells. Tissues from 94 patients with advanced epithelial ovarian cancer (EOC) and 30 ovarian cystadenomas were obtained. We analyzed the association of the immunohistochemical-determined expression of these two factors and clinicopathologic variables, overall survival, and angiogenesis. We established SKOV3 cells stably overexpressing XAF1 and explored the possible functions of XAF1 in ovarian cancer cells in vitro and in vivo. The protein expression of XAF1 was significantly lower and that of XIAP higher in malignant than nonmalignant tissues. Low XAF1 expression was associated with high-grade tumors and poor overall survival for patients. XAF1 expression was associated with microvessel density. Overexpression of XAF1 suppressed cell proliferation and enhanced SKOV3 cells sensitivity to cisplatin, as well as inhibited tumor growth and decreased MVD in vivo. Overexpression of XAF1 induced XIAP inactivation, caspase-3 activation and cytosolic expression of cytochrome c. These results suggested that XAF1 may be involved in ovarian cancer development and up-regulation of XAF1 may confer sensitivity of ovarian cancer cells to cisplatin-mediated apoptosis. (C) 2012 Elsevier B.V. All rights reserved.