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Network Pharmacology and Traditional Medicine

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Front. Pharmacol. | doi: 10.3389/fphar.2018.01106

Network pharmacology-based validation of caveolin-1 as a key mediator of Ai Du Qing inhibition of drug resistance in breast cancer

  • 1The Research Center for Integrative Medicine, Guangdong Provincial Academy of Chinese Medical Sciences, Guangzhou University of Chinese Medicine, China
  • 2Tropical Medicine Institute, Guangzhou University of Chinese Medicine, China
  • 3Integrative Research Laboratory of Breast Cancer, Discipline of Integrated Chinese and Western Medicine, Second Affiliated Hospital of Guangzhou Medical University, China

Chinese formulas have been paid increasing attention in cancer multidisciplinary therapy due to their multi-targets and multi-substances property. Here, we aim to investigate the anti-breast cancer and chemosensitizing function of Ai Du Qing (ADQ) formula made up of Hedyotis diffusa, Curcuma zedoaria (Christm.) Rosc., Astragalus membranaceus (Fisch.) Bunge and Glycyrrhiza uralensis Fisch. Our findings revealed that ADQ significantly inhibited cell proliferation in both parental and chemo-resistant breast cancer cells, but with little cytotoxcity effects on the normal cells. Besides, ADQ was found to facilitate the G2/M arresting and apoptosis induction effects of paclitaxel. Network pharmacology and bioinformatics analysis further demonstrated that ADQ yielded 132 candidate compounds and 297 potential targets, and shared 22 putative targets associating with breast cancer chemoresponse. Enrichment analysis and experimental validation demonstrated that ADQ might improve breast cancer chemosensitivity via inhibiting caveolin-1, which further triggered expression changes of cell cycle-related proteins p21/cyclinB1 and apoptosis-associated proteins PARP1, BAX and Bcl-2. Besides, ADQ enhanced in vivo paclitaxel chemosensitivity on breast cancer. Our study not only uncovers the novel function and mechanisms of ADQ in chemosensitizing breast cancer at least partly via targeting caveolin-1, but also sheds novel light in utilizing network pharmacology in Chinese Medicine research.

Keywords: breast cancer chemosensitivity, Network Pharmacology, Bioinformatics analysis, Ai Du Qing, caveolin-1

Received: 16 Apr 2018; Accepted: 10 Sep 2018.

Edited by:

Shi-Bing Su, Shanghai University of Traditional Chinese Medicine, China

Reviewed by:

Juntaro Matsuzaki, National Cancer Centre (Japan), Japan
Li-Wha Wu, National Cheng Kung University, Taiwan
Chuanbin Yang, Hong Kong Baptist University, Hong Kong  

Copyright: © 2018 Wang, Yang, Zhang, Wang, Zheng, Liu, Huang, Pan, Li, Zhang and Wang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Prof. Zhiyu Wang, Guangzhou University of Chinese Medicine, The Research Center for Integrative Medicine, Guangdong Provincial Academy of Chinese Medical Sciences, Guangzhou, China,