title: NF-κB suppresses apoptosis and promotes bladder cancer cell proliferation by upregulating survivin expression in vitro and in vivo.
abstract: 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.
authors.affiliation: Department of Urology, The First Hospital of China Medical University, Shenyang 110001, Liaoning, China.
authors.forename: Xiaolu
authors.initials: X
authors.lastname: Cui
authors.affiliation: Department of Urology, The First Hospital of China Medical University, Shenyang 110001, Liaoning, China.
authors.forename: Dezhi
authors.initials: D
authors.lastname: Shen
authors.affiliation: Department of Urology, The First Hospital of China Medical University, Shenyang 110001, Liaoning, China.
authors.forename: Chuize
authors.initials: C
authors.lastname: Kong
authors.affiliation: Department of Urology, The First Hospital of China Medical University, Shenyang 110001, Liaoning, China.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Urology, The First Hospital of China Medical University, Shenyang 110001, Liaoning, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zeng
authors.affiliation: Department of Pathology, The First Affiliated Hospital and College of Basic Medical Sciences, China Medical University, Shenyang 110001, Liaoning, China.
authors.forename: Xuyong
authors.initials: X
authors.lastname: Lin
authors.affiliation: Department of Urology, The First Hospital of China Medical University, Shenyang 110001, Liaoning, China.
authors.forename: Xiankui
authors.initials: X
authors.lastname: Liu
mesh_terms: D000328:Adult; D000368:Aged; D017209:Apoptosis / Q000235:genetics*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D017930:Genes, Reporter; D006801:Humans; D007150:Immunohistochemistry; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D016328:NF-kappa B / Q000378:metabolism*; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D015398:Signal Transduction; D000077022:Survivin; D015854:Up-Regulation; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology
chemical_list: C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D016328:NF-kappa B; D000077022:Survivin