文章基本信息

标题：NF-κB suppresses apoptosis and promotes bladder cancer cell proliferation by upregulating survivin expression in vitro and in vivo
本地全文：下载
作者：Xiaolu Cui ; Dezhi Shen ; Chuize Kong 等
期刊名称：Scientific Reports
电子版ISSN：2045-2322
出版年度：2017
卷号：7
期号：1
DOI：10.1038/srep40723
语种：English
出版社：Springer Nature
摘要：Nuclear factor kappa-B (NF-κB) activation is a common phenomenon in cancers, which results in the aberrant expression of NF-κB target genes and leads to malignant transformation, metastatic dissemination, abnormal cell proliferation or resistance to cell death. Survivin is a unique member of the IAP family, a well-known cancer-specific molecule and a molecular marker of poor clinical outcome in several cancer types, including bladder cancer. YM-155, a potent survivin suppressor, has been shown to have anti-tumor activity in preclinical cell lines, xenograft models and phase I/II studies. In the present study, we investigated the function of the NF-κB/survivin pathway in bladder cancer. We found that NF-κB can promote cell cycle progression and reduce apoptosis by upregulating survivin expression, thereby increasing cellular proliferation. We further confirmed the tumorigenic function of the NF-κB/survivin pathway in vivo using a xenograft tumor model of stable NF-κB-overexpressing 5637 cells. Moreover, we found that YM-155 significantly induced apoptosis and decreased cellular proliferation as well as tumor growth in mice. Our results demonstrate the carcinogenic function of the NF-κB/survivin pathway in bladder cancer and the role of YM-155 as a promising agent for the strategic treatment of bladder cancer.