國家衛生研究院 NHRI:Item 3990099045/4288
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    題名: The synergistic anticancer effect of troglitazone combined with aspirin causes cell cycle arrest and apoptosis in human lung cancer cells
    作者: Yan, KH;Yao, CJ;Chang, HY;Lai, GM;Cheng, AL;Chuang, SE
    貢獻者: National Institute of Cancer Research
    摘要: Troglitazone (TGZ) is a synthetic thiazolidinedione drug belonging to a group of potent peroxisome proliferator-activated receptor gamma (PPAR gamma) agonists known to inhibit proliferation, alter cell cycle regulation, and induce apoptosis in various cancer cell types. TGZ is an oral anti-type II diabetes drug that can reverse insulin resistance. For more then 100 yr, aspirin, a nonselective cyclooxygenase (COX) inhibitor, has been successfully used as an anti-inflammatory drug. Recently, Aspirin (ASA) and some other nonsteroidal anti-inflammatory drugs (NSAIDs) have drawn much attention for their protective effects against colon cancer and cardiovascular disease; it has been observed that ASA's anti-tumor effect can be attributed to inhibition of cell cycle progression, induction of apoptosis, and inhibition of angiogenesis. In this report we demonstrate for the first time that, when administered in combination, TGZ and ASA can produce a strong synergistic effect in growth inhibition and G(1) arrest in lung cancer CL1-0 and A549 cells. Examination by colony formation assay revealed an even more profound synergy. In Western blot, combined TGZ and ASA also could downregulate Cdk2, E2F-1, cyclin 81, cyclin D3 protein, and the ratio of phospho-Rb/Rb. importantly, apoptosis was synergistically induced by the combination treatment, as evidenced by caspase-3 activation and PARP cleavage. The involvement of PI3K/Akt inhibition and p27 upregulation, as well as hypophosphorylation of Rac1 at ser71, were demonstrated. Taken together, these results suggest that clinically achievable concentrations of TGZ and ASA used in combination may produce a strong anticancer synergy that warrants further investigation for its clinical applications.
    日期: 2010-03
    關聯: Molecular Carcinogenesis. 2010 Mar;49(3):235-246.
    Link to: http://dx.doi.org/10.1002/mc.20593
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0899-1987&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000275216500004
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=77949878222
    顯示於類別:[莊雙恩] 期刊論文
    [賴基銘(2004-2008)] 期刊論文

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