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Specific growth inhibition by alteration of metabolic pathway using Chinese herbal medicine in tyrosine kinase inhibitor resistant non-small cell lung cancer

引用

中国药理学与毒理学杂志 2015年第S1期29卷 85-86页

作者： Xing-xingFAN MariaPikWONG Zhi-weiCAO Jian-linWU HuaZHOU Zhi-hongJIANG LiangLIU ElaineLai-hanLEUNG State Key Laboratory of Quality Research in Chinese Medicine Macao Institute For Applied Research in Medicine and Health Macao University of Science and Technology Macao China Department of Pathology Li Ka Shing Faculty of Medicine University of Hong Kong Hong Kong China School of Life Science Tongji University Shanghai China

OBJECTIVE Lung cancer is the leading cause of cancer death *** growth factor receptor(EGFR)mutation(s)is/are common in non-small cell lung cancer(NSCLC)in Asian population,resulting in lung tumor formation.L858 Rsubstitution mutation on exon 21 and in-flame deletion mutation on exon 19 are the two most common forms of EGFR *** targeted therapy using tyrosine kinase inhibitor(TKI)targeting EGFR shows promising initial response,however drug resistance is ***,it is needed to identify new inhibitors to tackle *** this study,we aim to investigate the effect of multiple single purified compounds derived from Chinese herbal medicines(CMHs)on a panel of NSCLC cell lines with different EGFR mutational statuses and TKI *** also examine the biological functional effect and drug action mechanism of these cell lines after drug *** We have reviewed the literature and selected ten single purified compounds derived from CMHs which exhibited the highest potential of cancer suppression effect in *** have recruited three EGFR-dependent NSCLC cell lines for drug screening using cytotoxicity assay.A549 is used as EGFR wild-type *** TKI-resistant NSCLC cell lines were used,H1975 harbors double mutation(EGFRL858R+T790M)and H1650 harbors EGFRexon 19 deletion.H2228is a NSCLC cell line which harbours EML4-ALK fusion gene and was used as EGFR-independent cell line *** assay was used to determine the drug efficacy and IC50 *** functional assays including cell cycle arrest analysis and apoptosis assay was used to determine the biological effect after drug *** MTT assay revealed that six out of ten candidate agents showed significant cancer-inhibiting effects in H1650 and *** compounds exhibited IC50 value at micro-molar levels while another three compounds exhibited IC50 at as low as nano-molar *** compound exhibited specificity on EGFR-dependent NSCLC

关键词： non-small cell lung cancer EGFR TKI resistance,can

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