Hoffmann Else K, Lambert Ian H
Department of Biology, University of Copenhagen, , 13 Universitetsparken, Copenhagen Ø 2100, Denmark.
Philos Trans R Soc Lond B Biol Sci. 2014 Feb 3;369(1638):20130109. doi: 10.1098/rstb.2013.0109. Print 2014 Mar 19.
Multi-drug resistance (MDR) to chemotherapy is the major challenge in the treatment of cancer. MDR can develop by numerous mechanisms including decreased drug uptake, increased drug efflux and the failure to undergo drug-induced apoptosis. Evasion of drug-induced apoptosis through modulation of ion transporters is the main focus of this paper and we demonstrate how pro-apoptotic ion channels are downregulated, while anti-apoptotic ion transporters are upregulated in MDR. We also discuss whether upregulation of ion transport proteins that are important for proliferation contribute to MDR. Finally, we discuss the possibility that the development of MDR involves sequential and localized upregulation of ion channels involved in proliferation and migration and a concomitant global and persistent downregulation of ion channels involved in apoptosis.
对化疗的多药耐药性（MDR）是癌症治疗中的主要挑战。MDR可通过多种机制产生，包括药物摄取减少、药物外排增加以及无法发生药物诱导的凋亡。通过调节离子转运体逃避药物诱导的凋亡是本文的主要关注点，我们展示了促凋亡离子通道在MDR中如何下调，而抗凋亡离子转运体如何上调。我们还讨论了对增殖重要的离子转运蛋白的上调是否促成MDR。最后，我们讨论了MDR的发展是否涉及参与增殖和迁移的离子通道的顺序性和局部上调以及参与凋亡的离子通道的伴随性全局和持续性下调的可能性。
