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BMC Complement Altern Med. 2018 Nov 6;18(1):293. doi: 10.1186/s12906-018-2347-x.

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

Bing Z1,2,3, Cheng Z1,2, Shi D4, Liu X5, Tian J1,2, Yao X4, Zhang J1,2, Wang Y6, Yang K7,8.

Author information

1
Evidence Based Medicine Center, School of Basic Medical Science of Lanzhou University, Lanzhou, China.
2
Key Laboratory of Evidence Based Medicine and Knowledge Translation of Gansu Province, 199 West Donggang Road, Lanzhou, 730000, Gansu, China.
3
Institute of Modern Physics of Chinese Academy of Sciences, Lanzhou, Gansu Province, China.
4
Department of Chemistry, State Key Laboratory of Applied Organic Chemistry, Lanzhou University, Lanzhou, China.
5
Department of Clinical Chinese Pharmacy, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, China.
6
Gansu University of Chinese Medicine, Lanzhou, China.
7
Evidence Based Medicine Center, School of Basic Medical Science of Lanzhou University, Lanzhou, China. kehuyangebm2006@126.com.
8
Key Laboratory of Evidence Based Medicine and Knowledge Translation of Gansu Province, 199 West Donggang Road, Lanzhou, 730000, Gansu, China. kehuyangebm2006@126.com.

Abstract

BACKGROUND:

Chinese 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.

METHODS:

A 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.

RESULTS:

The 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.

CONCLUSIONS:

This study provided a workflow for understanding mechanism of CHM for against drug resistance.

KEYWORDS:

Fuzhengkangai formula; Herbal medicines; Molecular docking; Systems pharmacology

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