生存素
藤黄酸
阿霉素
细胞凋亡
细胞内
癌症研究
癌细胞
P-糖蛋白
凋亡抑制因子
p38丝裂原活化蛋白激酶
化学
活性氧
药理学
癌症
乳腺癌
夏普
Abcg2型
抗药性
MAPK/ERK通路
多重耐药
程序性细胞死亡
生物
医学
化疗
信号转导
ATP结合盒运输机
半胱氨酸蛋白酶
运输机
生物化学
内科学
微生物学
基因
作者
Shengpeng Wang,Lu Wang,Meiwan Chen,Ying Wang
标识
DOI:10.1016/j.cbi.2015.03.017
摘要
The development of resistance to chemotherapeutic agents remains a major challenge to breast cancer chemotherapy. Overexpression of drug efflux transporters like P-glycoprotein (P-gp) and resistance to apoptosis are the two key factors that confer cancer drug resistance. Gambogic acid (GA), a major component of Gamboge resin, has potent anticancer effects and can inhibit the growth of several types of human cancers. However, the potential and underlying mechanisms of GA in reversing cancer resistance remain poorly understood. In the present study, we found that GA can markedly sensitize doxorubicin (DOX)-resistant breast cancer cells to DOX-mediated cell death. GA increased the intracellular accumulation of DOX by inhibiting both P-gp expression and activity. Meanwhile, the combination effect was associated with the generation of intracellular reactive oxygen species (ROS) and the suppression of anti-apoptotic protein survivin. Scavenging intracellular ROS or overexpression of survivin blocked the sensitizing effects of GA in DOX-induced apoptosis. Furthermore, ROS-mediated activation of p38 MAPK was revealed in GA-mediated suppression of survivin expression. This study gives rise to the possibility of applying GA as an anticancer agent for the purpose of combating DOX-resistant breast cancer.
科研通智能强力驱动
Strongly Powered by AbleSci AI