Predicting drug sensitivity and resistance:: Profiling ABC transporter genes in cancer cells
Predicting drug sensitivity and resistance:: Profiling ABC transporter genes in cancer cells
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DOI：
10.1016/j.ccr.2004.06.026
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发表时间：
2004-08-01
期刊：
影响因子：
50.3
通讯作者：
Gottesman, MM
中科院分区：
文献类型：
--
作者：
Szakács, G;Annereau, JP;Gottesman, MM
为了分析多药耐药性，有效的癌症化疗的主要障碍，我们分析了48种已知的人类ABC转运蛋白在60种不同的癌细胞系（NCI-60）中的mRNA表达，这些癌细胞系由美国国家癌症研究所用于筛选抗癌活性。实时RT-PCR的使用避免了微阵列技术通常遇到的伪影。通过将结果与针对细胞测试的1，429种候选抗癌药物的生长抑制特征相关联，我们确定了哪些转运蛋白比其他转运蛋白更有可能对哪些药物产生耐药性。出乎意料的是，我们还发现并验证了其活性被MDR 1多药转运蛋白增强而不是拮抗的化合物。这些化合物可以作为开发的先导。
For analysis of multidrug resistance, a major barrier to effective cancer chemotherapy, we profiled mRNA expression of the 48 known human ABC transporters in 60 diverse cancer cell lines (the NCI-60) used by the National Cancer Institute to screen for anticancer activity. The use of real-time RT-PCR avoided artifacts commonly encountered with microarray technologies. By correlating the results with the growth inhibitory profiles of 1,429 candidate anticancer drugs tested against the cells, we identified which transporters are more likely than others to confer resistance to which agents. Unexpectedly, we also found and validated compounds whose activity is potentiated, rather than antagonized, by the MDR1 multidrug transporter. Such compounds may serve as leads for development.