Investigate the mechanisms of Chinese medicine Fuzhengkangai towards EGFR mutation-positive lung adenocarcinomas by network pharmacology

doi:10.1186/s12906-018-2347-x

	Investigate the mechanisms of Chinese medicine Fuzhengkangai towards EGFR mutation-positive lung adenocarcinomas by network pharmacology
	Bing, Zhitong1,2,3 ; Cheng, Zhiyuan 1,2; Shi, Danfeng 4; Liu, Xinkui 5; Tian, Jinhui 1,2; Yao, Xiaojun 4; Zhang, Jingyun 1,2; Wang, Yongfeng 6; Yang, Kehu 1,2
刊名	BMC COMPLEMENTARY AND ALTERNATIVE MEDICINE
	2018-11-06
卷号	18
关键词	Systems pharmacology Fuzhengkangai formula Herbal medicines Molecular docking
ISSN号	1472-6882
DOI	10.1186/s12906-018-2347-x
英文摘要	BackgroundChinese traditional herbal medicine Fuzhengkangai (FZKA) formulation combination with gefitinib can overcome drug resistance and improve the prognosis of lung adenocarcinoma patients. However, the pharmacological and molecular mechanisms underlying the active ingredients, potential targets, and overcome drug resistance of the drug are still unclear. Therefore, it is necessary to explore the molecular mechanism of FZKA.MethodsA systems pharmacology and bioinformatics-based approach was employed to investigate the molecular pathogenesis of EGFR-TKI resistance with clinically effective herb formula. The differential gene expressions between EGFR-TKI sensitive and resistance cell lines were calculated and used to find overlap from targets as core targets. The prognosis of core targets was validated from the cancer genome atlas (TCGA) database by Cox regression. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment is applied to analysis core targets for revealing mechanism in biology.ResultsThe results showed that 35 active compounds of FZKA can interact with eight core targets proteins (ADRB2, BCL2, CDKN1A, HTR2C, KCNMA1, PLA2G4A, PRKCA and LYZ). The risk score of them were associated with overall survival and relapse free time (HR=6.604, 95% CI: 2.314-18.850; HR=5.132, 95% CI: 1.531-17.220). The pathway enrichment suggested that they involved in EGFR-TKI resistance and non-small cell lung cancer pathways, which directly affect EGFR-TKI resistance. The molecular docking showed that licochalcone a and beta-sitosterol can closely bind two targets (BCL2 and PRKCA) that involved in EGFR-TKI resistance pathway.ConclusionsThis study provided a workflow for understanding mechanism of CHM for against drug resistance.
资助项目	Gansu province funding[1606RJZA016]
WOS关键词	ACQUIRED-RESISTANCE ; UP-REGULATION ; CANCER ; GEFITINIB ; AMPLIFICATION ; CHEMOTHERAPY ; ERLOTINIB ; BCL-2 ; POLYMORPHISM ; ACTIVATION
WOS研究方向	Integrative & Complementary Medicine
语种	英语
出版者	BMC
WOS记录号	WOS:000449341600003
内容类型	期刊论文
源URL	[http://119.78.100.186/handle/113462/64417]
专题	中国科学院近代物理研究所
通讯作者	Yang, Kehu
作者单位	1.Lanzhou Univ, Sch Basic Med Sci, Evidence Based Med Ctr, Lanzhou, Gansu, Peoples R China 2.Lab Evidence Based Med & Knowledge Translat Gansu, 199 West Donggang Rd, Lanzhou 730000, Gansu, Peoples R China 3.Chinese Acad Sci, Inst Modern Phys, Lanzhou, Gansu, Peoples R China 4.Lanzhou Univ, State Key Lab Appl Organ Chem, Dept Chem, Lanzhou, Gansu, Peoples R China 5.Beijing Univ Chinese Med, Sch Chinese Mat Med, Dept Clin Chinese Pharm, Beijing, Peoples R China 6.Gansu Univ Chinese Med, Lanzhou, Gansu, Peoples R China
推荐引用方式 GB/T 7714	Bing, Zhitong,Cheng, Zhiyuan,Shi, Danfeng,et al. Investigate the mechanisms of Chinese medicine Fuzhengkangai towards EGFR mutation-positive lung adenocarcinomas by network pharmacology[J]. BMC COMPLEMENTARY AND ALTERNATIVE MEDICINE,2018,18.
APA	Bing, Zhitong.,Cheng, Zhiyuan.,Shi, Danfeng.,Liu, Xinkui.,Tian, Jinhui.,...&Yang, Kehu.(2018).Investigate the mechanisms of Chinese medicine Fuzhengkangai towards EGFR mutation-positive lung adenocarcinomas by network pharmacology.BMC COMPLEMENTARY AND ALTERNATIVE MEDICINE,18.
MLA	Bing, Zhitong,et al."Investigate the mechanisms of Chinese medicine Fuzhengkangai towards EGFR mutation-positive lung adenocarcinomas by network pharmacology".BMC COMPLEMENTARY AND ALTERNATIVE MEDICINE 18(2018).