Stavrovskaya A A, Rybalkina E Yu
Blokhin Medical Research Center of Oncology, Ministry of Health of the Russian Federation, Moscow, 115478, Russia.
Biochemistry (Mosc). 2018 Jul;83(7):779-786. doi: 10.1134/S0006297918070015.
Here we present new approaches to better understanding multidrug resistance (MDR) development in cancer cells, such as identification of components of a complex process of MDR evolution. Recent advances in the studies of MDR are discussed: 1) chemotherapy agents might be involved in the selection of cancer stem cells resulting in the elevated drug resistance and enhanced tumorigenicity; 2) cell-cell interactions have a great effect on the MDR emergence and evolution; 3) mechanotransduction is an important signaling mechanism in cell-cell interactions; 4) proteins of the ABC transporter family which are often involved in MDR might be transferred between cells via microvesicles (epigenetic MDR regulation); 5) proteins providing cell-to-cell transfer of functional P-glycoprotein (MDR1 protein) via microvesicles have been investigated; 6) P-glycoprotein may serve to regulate apoptosis, as well as transcription and translation of target genes/proteins. Although proving once again that MDR is a complex multi-faceted process, these data open new approaches to overcoming it.
在此,我们提出了一些新方法,以更好地理解癌细胞中多药耐药性(MDR)的产生,例如识别MDR演变这一复杂过程的组成部分。本文讨论了MDR研究的最新进展:1)化疗药物可能参与了癌症干细胞的选择,导致耐药性升高和肿瘤发生能力增强;2)细胞间相互作用对MDR的出现和演变有很大影响;3)机械转导是细胞间相互作用中的一种重要信号传导机制;4)通常参与MDR的ABC转运蛋白家族的蛋白质可能通过微泡在细胞间转移(表观遗传MDR调节);5)已经研究了通过微泡提供功能性P-糖蛋白(MDR1蛋白)细胞间转移的蛋白质;6)P-糖蛋白可能用于调节细胞凋亡以及靶基因/蛋白质的转录和翻译。尽管再次证明MDR是一个复杂的多方面过程,但这些数据为克服它开辟了新方法。