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BMC Complementary Medicine and Therapies
Published in: BMC Complementary Medicine and Therapies 1/2018

Open Access 01-12-2018 | Research article

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

Authors: Zhitong Bing, Zhiyuan Cheng, Danfeng Shi, Xinkui Liu, Jinhui Tian, Xiaojun Yao, Jingyun Zhang, Yongfeng Wang, Kehu Yang

Published in: BMC Complementary Medicine and Therapies | Issue 1/2018

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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.
Appendix
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Metadata
Title
Investigate the mechanisms of Chinese medicine Fuzhengkangai towards EGFR mutation-positive lung adenocarcinomas by network pharmacology
Authors
Zhitong Bing
Zhiyuan Cheng
Danfeng Shi
Xinkui Liu
Jinhui Tian
Xiaojun Yao
Jingyun Zhang
Yongfeng Wang
Kehu Yang
Publication date
01-12-2018
Publisher
BioMed Central
Published in
BMC Complementary Medicine and Therapies / Issue 1/2018
Electronic ISSN: 2662-7671
DOI
https://doi.org/10.1186/s12906-018-2347-x

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