The effects and mechanisms of aloe-emodin on reversing adriamycin-induced resistance of MCF-7/ADR cells
The effects and mechanisms of aloe-emodin on reversing adriamycin-induced resistance of MCF-7/ADR cells
复制标题
芦荟大黄素逆转阿霉素诱导的MCF-7/ADR细胞耐药的作用及机制
DOI：
10.1002/ptr.7096
复制
发表时间：
2021-03-31
影响因子：
7.2
通讯作者：
Song, Fengrui
中科院分区：
文献类型：
--
作者：
Cheng, Guorong;Pi, Zifeng;Song, Fengrui
Multidrug resistance (MDR) is one of the major obstacles for clinical effective chemotherapy. In this study, the effects and possible mechanisms of aloe-emodin (AE) were investigated on reversing the adriamycin (ADR)-induced resistance of MCF-7/ADR cells. AE could significantly reverse the ADR resistance in MCF-7/ADR cells. The combination of AE (20 mu M) and ADR had no effect on the P-glycoprotein (P-gp) level, but notably promoted the accumulation of ADR in drug-resistant cells. The efflux function of P-gp required ATP, but AE reduced the intracellular ATP level. AE played a reversal role might through inhibiting the efflux function of P-gp. The research result of energy metabolism pathways indicated that combination of AE and ADR could inhibit glycolysis, tricarboxylic acid (TCA) cycle, glutamine metabolism, and related amino acid synthesis pathways. Moreover, we found AE not only reversed ADR-induced resistant but also induced autophagy as a defense mechanism. In addition, the combination of AE and ADR arrested G2/M cell cycle and induced apoptosis through DNA damage, ROS generation, caspase-3 activation. Our study indicated that AE could be a potential reversal agent to resensitize ADR resistant in tumor chemotherapy and inhibiting autophagy might be an effective strategy to further enhance the reversal activity of AE.
