國家衛生研究院 NHRI:Item 3990099045/2773
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    題名: Increase of the resistance of human cervical carcinoma cells to cisplatin by inhibition of the MEK to ERK signaling pathway partly via enhancement of anticancer drug-induced NF kappa B activation
    其他題名: Increase of the resistance of human cervical carcinoma cells to cisplatin by inhibition of the MEK to ERK signaling pathway partly via enhancement of anticancer drug-induced NFκB activation
    作者: Yeh, PY;Chuang, SE;Yeh, KH;Song, YC;Ea, CK;Cheng, AL
    貢獻者: National Institute of Cancer Research
    摘要: In this study, we showed that suppression of the MEK-ERK transduction pathway by a selective inhibitor, 2-amino-3'-methoxyflavone (PD98059), increased drug resistance of SiHa cells to cisplatin, but not to another common anticancer drug, doxorubicin. The downstream mechanism of this discrepant cellular response was investigated. Both cisplatin and doxorubicin activated nuclear ERK2 and nuclear transcription factor kappaB (NFkappaB) of SiHa cells. However, suppression of the MEK-ERK2 pathway by PD98059 resulted in a further enhancement of cisplatin-induced NFkappaB activation, while no further regulation of NFkappaB was noted in doxorubicin-treated cells. The activation of NFkappaB by cisplatin or doxorubicin was not due to the degradation of cytoplasmic IkappaBalpha, as demonstrated by western blotting. Transfection of a dominant negative IkappaBalpha resulted in a markedly diminished PD98059-induced cisplatin resistance in SiHa cells. Our results suggest that the MEK-ERK signaling pathway plays a role in the chemosensitivity of SiHa cells, and suppression of this pathway increases cisplatin resistance partly via an increase of NFkappaB activation. The mechanism responsible for the discrepant effect of PD98059 on NFkappaB activation and hence the chemo sensitivity of SiHa cells towards cisplatin and doxorubicin remains to be investigated. (C) 2002 Elsevier Science Inc, All rights reserved.
    關鍵詞: Pharmacology & Pharmacy
    日期: 2002-04-15
    關聯: Biochemical Pharmacology. 2002 Apr;63(8):1423-1430.
    Link to: http://dx.doi.org/10.1016/S0006-2952(02)00908-5
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0006-2952&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000176419600006
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=0037091048
    顯示於類別:[莊雙恩] 會議論文/會議摘要

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