Reversal of doxorubicin resistance in lung cancer cells by neferine is explained by nuclear factor erythroid-derived 2-like 2 mediated lung resistance protein down regulation  

作　　者：Poornima Paramasivan Jothi Dinesh Kumar Rathinasamy Baskaran Ching Feng Weng Viswanadha Vijaya Padma 

机构地区：[1]Department of Biotechnology,School of Biotechnology and Genetic Engineering,Bharathiar University,Coimbatore,Tamil Nadu 641046,India. [2]Department of Cellular and Molecular Physiology,Institute of Translational Medicine,University of Liverpool,Liverpool L35TR,UK. [3]Laboratory of Molecular Physiology,Institute of Biotechnology,Department of Life Sciences,National Dong Hwa University,Hualien 974,Taiwan. [4]Division of Science,School of Applied Sciences,University of Abertay Dundee,Dundee DD11HG,UK. [5]Department of Bioinformatics and Medical Engineering,Asia University,Taichung 41354,Taiwan.

出　　处：《Cancer Drug Resistance》2020年第3期647-665,共19页癌症耐药（英文）

摘　　要：Aim:Development of multi drug resistance and dose limiting cardiotoxicity are hindering the use of Doxorubicin(Dox)in clinical settings.Augmented dox efflux induced by lung resistance protein(LRP)over expression has been related to multi drug resistance phenotype in various cancers.An alkaloid from lotus,Neferine(Nef)shows both anticancer and cardioprotective effects.Here,we have investigated the interconnection between nuclear factor erythroid-derived 2-like 2(NRF2)and LRP in Dox resistance and how Nef can overcome Dox resistance in lung cancer cells by altering this signaling.Methods:Anti-proliferative and apoptotic-inducing effects of Nef and Dox combination in Parental and Dox resistant lung cancer cells were determined in monolayers and 3D spheroids.Intracellular Dox was analyzed using flow cytometry,siRNA knockdown and western blot analysis were used to elucidate NRF2-LRP crosstalk mechanism.

关 键 词：DOXORUBICIN NEFERINE reactive oxygen species lung resistance protein nuclear factor erythroid-derived 2-like 2 multidrug resistance 

分 类 号：R73[医药卫生—肿瘤]