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Front Pharmacol. 2018 Dec 17;9:1473. doi: 10.3389/fphar.2018.01473. eCollection 2018.

A Novel Systems Pharmacology Method to Investigate Molecular Mechanisms of Scutellaria barbata D. Don for Non-small Cell Lung Cancer.

Author information

1
Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, School of Life Sciences, Northwest University, Xi'an, China.
2
Pharmacology Department, School of Pharmacy, Shihezi University, Shihezi, China.
3
State Key Laboratory of New-tech for Chinese Medicine Pharmaceutical Process, Jiangsu Kanion Parmaceutical, Co., Ltd., Lianyungang, China.

Abstract

Non-small cell lung cancer (NSCLC) is the most ordinary type of lung cancer which leads to 1/3 of all cancer deaths. At present, cytotoxic chemotherapy, surgical resection, radiation, and photodynamic therapy are the main strategies for NSCLC treatment. However, NSCLC is relatively resistant to the above therapeutic strategies, resulting in a rather low (20%) 5-year survival rate. Therefore, there is imperative to identify or develop efficient lead compounds for the treatment of NSCLC. Here, we report that the herb Scutellaria barbata D. Don (SBD) can effectively treat NSCLC by anti-inflammatory, promoting apoptosis, cell cycle arrest, and angiogenesis. In this work, we analyze the molecular mechanism of SBD for NSCLC treatment by applying the systems pharmacology strategy. This method combines pharmacokinetics analysis with pharmacodynamics evaluation to screen out the active compounds, predict the targets and assess the networks and pathways. Results show that 33 compounds were identified with potential anti-cancer effects. Utilizing these active compounds as probes, we predicted that 145 NSCLC related targets mainly involved four aspects: apoptosis, inflammation, cell cycle, and angiogenesis. And in vitro experiments were managed to evaluate the reliability of some vital active compounds and targets. Overall, a complete overview of the integrated systems pharmacology method provides a precise probe to elucidate the molecular mechanisms of SBD for NSCLC. Moreover, baicalein from SBD effectively inhibited tumor growth in an LLC tumor-bearing mice models, demonstrating the anti-tumor effects of SBD. Our findings further provided experimental evidence for the application in the treatment of NSCLC.

KEYWORDS:

Scutellaria barbata D. Don; baicalein; non-small cell lung cancer; systems pharmacology; the molecular mechanism

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