NF-?B suppresses apoptosis and promotes bladder cancer cell proliferation by upregulating survivin expression in vitro and in vivo.

ABSTRACT: Nuclear factor kappa-B (NF-?B) activation is a common phenomenon in cancers, which results in the aberrant expression of NF-?B 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-?B/survivin pathway in bladder cancer. We found that NF-?B 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-?B/survivin pathway in vivo using a xenograft tumor model of stable NF-?B-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-?B/survivin pathway in bladder cancer and the role of YM-155 as a promising agent for the strategic treatment of bladder cancer.

SUBMITTER: Cui X 

PROVIDER: S-EPMC5282527 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature