Murphy L, Clynes M, Keenan J
National Institute of Cellular Biology, Dublin City University, Ireland.
Anticancer Res. 2007 May-Jun;27(3A):1277-84.
Mitoxantrone resistance has been related to the expression of a drug efflux pump breast cancer resistance pump (BCRP) but little is known of the intracellular protein changes. In this work, differential protein expression in a squamous lung carcinoma cell line, DLKP, and its mitoxantrone-resistant variant (DLKP-Mitox) was investigated to elucidate other changes associated with mitoxantrone resistance.
Differential protein expression between DLKP and DLKP-Mitox was investigated using 2D-DIGE technology. Proteins of interest were identified by MALDI-ToF mass spectrometry. Western blotting was used to confirm and validate some of these changes.
Biological variation analysis in Decyder software revealed a total of 343 proteins to be differentially regulated with p < 0.05. Identification of 61 proteins of interest by mass spectrometry revealed changes in proteins involved in many cellular processes including apoptosis and differentiation.
Alterations in these cellular processes and proteins present alternative sites to circumvent resistance to mitoxantrone.
米托蒽醌耐药性与一种药物外排泵——乳腺癌耐药蛋白（BCRP）的表达有关，但细胞内蛋白质变化情况鲜为人知。在本研究中，对一种肺鳞癌细胞系DLKP及其米托蒽醌耐药变体（DLKP-Mitox）的蛋白质表达差异进行了研究，以阐明与米托蒽醌耐药相关的其他变化。
采用二维差异凝胶电泳（2D-DIGE）技术研究DLKP和DLKP-Mitox之间的蛋白质表达差异。通过基质辅助激光解吸电离飞行时间质谱（MALDI-ToF）鉴定感兴趣的蛋白质。利用蛋白质免疫印迹法对其中一些变化进行确认和验证。
Decyder软件中的生物学差异分析显示，共有343种蛋白质的表达差异具有统计学意义（p < 0.05）。通过质谱鉴定出61种感兴趣的蛋白质，结果显示参与包括凋亡和分化在内的许多细胞过程的蛋白质发生了变化。
这些细胞过程和蛋白质的改变为克服米托蒽醌耐药性提供了新的靶点。
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