文献类型：期刊文献

英文题名：Chaetominine reduces MRP1-mediated drug resistance via inhibiting PI3K/Akt/Nrf2 signaling pathway in K562/Adr human leukemia cells

作者：Yao, Jingyun[1,2];Wei, Xing[1,2];Lu, Ynhua[1,2]

机构：[1]E China Univ Sci & Technol, State Key Lab Bioreactor Engn, Box 283,130 Meilong Rd, Shanghai 200237, Peoples R China;[2]Shanghai Collaborat Innovat Ctr Biomfg Technol, 130 Meilong Rd, Shanghai, Peoples R China

年份：2016

卷号：473

期号：4

起止页码：867

外文期刊名：BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000375823700015)】；

基金：This work was supported by the National High Technology Research and Development Program of China (2013AA092901), and partially financed by the Fundamental Research Funds for the Central Universities (WF1113010), the National Special Fund for State Key Laboratory of Bioreactor Engineering (2060204).

语种：英文

外文关键词：Chaetominine; Reversal effect; Chemoresistance; K562/Adr; MRP1

摘要：Drug resistance limits leukemia treatment and chaetominine, a cytotoxic alkaloid that promotes apoptosis in a K562 human leukemia cell line via the mitochondrial pathway was studied with respect to chemoresistance in a K562/Adr human resistant leukemia cell line. Cytotoxicity assays indicated that K562/Adr resistance to adriamycin (ADR) did not occur in the presence of chaetominine and that chaetominine increased chemosensitivity of K562/Adr to ADR. Data show that chaetominine enhanced ADR-induced apoptosis and intracellular ADR accumulation in K562/Adr cells. Accordingly, chaetominine induced apoptosis by upregulating ROS, pro-apoptotic Bax and downregulating anti-apoptotic Bcl-2. RT-PCR and western-blot confirmed that chaetominine suppressed highly expressed MRP1 at mRNA and protein levels. But little obvious alternation of another drug transporter MDR1 mRNA was observed. Furthermore, inhibition of MRP1 by chaetominine relied on inhibiting Akt phosphorylation and nuclear Nrf2. In summary, chaetominine strongly reverses drug resistance by interfering with the PI3K/Akt/Nrf2 signaling, resulting in reduction of MRP1-mediated drug efflux and induction of Bax/Bcl-2-dependent apoptosis in an ADR-resistant K562/Adr leukemia cell line. (C) 2016 Elsevier Inc. All rights reserved.