國家衛生研究院 NHRI:Item 3990099045/2699
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    题名: Inhibition of cell growth and nuclear factor-kappa B activity in pancreatic cancer cell lines by a tylophorine analogue, DCB-3503
    作者: Shiah, HS;Gao, WL;Baker, DC;Cheng, YC
    贡献者: National Institute of Cancer Research
    摘要: A tylophorine analogue, DCB-3503, has been shown to have potent activity against tumor growth in vitro and in vivo, as well as activity in an autoimmune disease model in vivo. This study focuses on investigating the mechanisms responsible for antitumor activity of DCB-3503. The concentrations for inhibiting 50% growth/colony formation ability are 50/162 and 40/149 nmol/L for PANC-1 and HPAC cells, respectively. The growth inhibition effects are associated with DCB-3503-induced reprogramming of tumor cells. DCB-3503 could interfere with cell cycle progression. Several cell cycle regulatory proteins, including cyclin D-1, are down-regulated by DCB-3503. Using several different transcription elements coupled with a reporter gene, it was found that the nuclear factor-kappa B (NF-kappa B) signaling pathway is the most sensitive pathway mediator affected by DCB-3503. The inhibition of NF-kappa B activity is dependent on the down-regulation of nuclear phosphorylated p65, a component of the active form of the NF-kappa B complex. Such a decrease in nuclear phosphorylated p65 can be reversed by a proteosome inhibitor. Furthermore, the activity and protein expression of nuclear I kappa B kinase alpha, which is responsible for p65 phosphorylation, is suppressed and down-regulated in cells treated with DCB-3503. In summary, DCB-3503 could affect cell cycle regulatory proteins and is a potent modulator of NF-kappa B function. It is a potentially useful compound in the management of cancers in which cyclin D1 overexpression and high NF-kappa B activity play a pivotal role.
    关键词: Oncology
    日期: 2006-10
    關聯: Molecular Cancer Therapeutics. 2006 Oct;5(10):2484-2493.
    Link to: http://dx.doi.org/10.1158/1535-7163.MCT-06-0146
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=1535-7163&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000241335600007
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=33750457941
    显示于类别:[夏和雄(1996-2012)] 期刊論文

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