Investigate the mechanisms of Chinese medicine Fuzhengkangai towards EGFR mutation-positive lung adenocarcinomas by network pharmacology
文献类型：期刊论文
| 作者 | Bing, Zhitong1,2,3 ; Cheng, Zhiyuan1,2; Shi, Danfeng4; Liu, Xinkui5; Tian, Jinhui1,2; Yao, Xiaojun4; Zhang, Jingyun1,2; Wang, Yongfeng6; Yang, Kehu1,2
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| 刊名 | BMC COMPLEMENTARY AND ALTERNATIVE MEDICINE
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| 出版日期 | 2018-11-06 |
| 卷号 | 18 |
| ISSN号 | 1472-6882 |
| 关键词 | Systems pharmacology Fuzhengkangai formula Herbal medicines Molecular docking |
| 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. |
| WOS关键词 | ACQUIRED-RESISTANCE ; UP-REGULATION ; CANCER ; GEFITINIB ; AMPLIFICATION ; CHEMOTHERAPY ; ERLOTINIB ; BCL-2 ; POLYMORPHISM ; ACTIVATION |
| 资助项目 | Gansu province funding[1606RJZA016] |
| WOS研究方向 | Integrative & Complementary Medicine |
| 语种 | 英语 |
| 出版者 | BMC |
| WOS记录号 | WOS:000449341600003 |
| 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). |
入库方式： OAI收割
来源：近代物理研究所
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