國家衛生研究院 NHRI:Item 3990099045/11706
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    题名: Erlotinib completely reverses topotecan-resistance in multidrug resistant cancer cells overexpressing breast cancer resistant protein 1
    作者: Yang, CH;Yang, CS;Huang, CJ;Cheng, AL;Whang-Peng, J;Yang, PC
    贡献者: National Institute of Cancer Research
    摘要: Erlotinib inhibits the ATP-binding site of the tyrosine kinase associated with the epidermal growth factor receptor. We have recently demonstrated that gefitinib, a structurally similar receptor tyrosine kinase inhibitor, inhibited functions of ATP-binding cassette transporters. The objective of this study is to explore the combined effect of erlotinib and chemotherapeutic agents in cells that overexpress ATP-binding cassette transporters. Cells that overexpress p-glycoprotein (MCF7/Adr and CL1/Pac), breast cancer resistant protein (MCF7/TPT300 and CL1/Tpt) and multidrug resistant-associated protein 1 (MCF7/Vp) were used in this study. All resistant mutants were insensitive to erlotinib. Erlotinib (0.3 to 3 μM) added to culture media had no effect on 50% inhibitory concentrations of paclitaxel, doxorubicin or etoposide in wild type MCF7 or CL1 cells. Erlotinib was synergistic with topotecan in CL1/WT cells. These concentrations of erlotinib also caused a dose-dependent reversal of resistance to topotecan in CL1/Tpt and MCF7/TPT cells. At 3μM, erlotinib completely reversed BCRP conferred topotecan resistance in these two chemoresistant cells. Erlotinib had only small reversing effect in p-glycoprotein or MRP1 overexpressing multidrug resistant cancer cells. Topotecan efflux was inhibited and accumulation was restored in CL1/Tpt and MCF7/TPT cells when cells were incubated simultaneously with 3μM of erlotinib. Our results suggest that erlotinib at a clinical attainable concentration completely reverses ABCG2 conferred resistance in multidrug resistant lung adenocarcinoma cancer cells.
    日期: 2006-04
    關聯: Cancer Research. 2006 Apr;66(8, Suppl.):1273-1274.
    Link to: http://cancerres.aacrjournals.org/content/66/8_Supplement/1273.4
    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:000454608804449
    显示于类别:[彭汪嘉康(1996-2007)] 會議論文/會議摘要

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