國家衛生研究院 NHRI:Item 3990099045/2782
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    Please use this identifier to cite or link to this item: http://ir.nhri.org.tw/handle/3990099045/2782


    Title: Sulfasalazine suppresses drug resistance and invasiveness of lung adenocarcinoma cells expressing AXL
    Other Titles: Sulfasalazine suppresses drug resistance and invasiveness of lung adenocarcinorna cells expressing AXL
    Authors: Lay, JD;Hong, CC;Huang, JS;Yang, YY;Pao, CY;Liu, CH;Lai, YP;Lai, GM;Cheng, AL;Su, IJ;Chuang, SE
    Contributors: National Institute of Cancer Research;Division of Clinical Research
    Abstract: Metastasis and drug resistance are the major causes of mortality in patients with non-small cell lung cancer (NSCLC). Several receptor tyrosine kinases (RTKs), including AXL, are involved in the progression of NSCLC. The AXL/MER/SKY subfamily is involved in cell adhesion, motility, angiogenesis, and signal transduction and may play a significant role in the invasiveness of cancer cells. Notably, no specific inhibitors of AXL have been described. A series of CL1 sublines with progressive invasiveness established from a patient with NSCLC has been identified that positively correlates with AXL expression and resistance to chemotherapeutic drugs. The ectopic overexpression of AXL results in elevated cell invasiveness and drug resistance. Nuclear factor-kappa B (NF-kappa B) signaling activity is associated with AXL expression and may play an important role in the enhancement of invasiveness and doxorubicin resistance, as shown by using the NF-kappa B inhibitor, sulfasalazine, and I kappa B dominant-negative transfectants. In the current study, sulfasalazine exerted a synergistic anticancer effect with doxorubicin and suppressed cancer cell invasiveness in parallel in CL1 sublines and various AXL-expressing cancer cell lines. Phosphorylation of AXL and other RTKs (ErbB2 and epidermal growth factor receptor) was abolished by sulfasalazine within 15 min, suggesting that the inhibition of NF-kappa B and the kinase activity of RTKs are involved in the pharmacologic effects of sulfasalazine. Our study suggests that AXL is involved in NSCLC metastasis and drug resistance and may therefore provide a molecular basis for RTK-targeted therapy using sulfasalazine to enhance the efficacy of chemotherapy in NSCLC.
    Keywords: Oncology
    Date: 2007-04-15
    Relation: Cancer Research. 2007 Apr;67(8):3878-3887.
    Link to: http://dx.doi.org/10.1158/0008-5472.CAN-06-3191
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0008-5472&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000245779600052
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=34248562252
    Appears in Collections:[Shuang-En Chuang] Periodical Articles
    [Ih-Jen Su(2002-2015)] Periodical Articles
    [Gi-Ming Lai(2004-2008)] Periodical Articles

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