Int J Biol Sci 2019; 15(7):1500-1513. doi:10.7150/ijbs.33146

Research Paper

Scutellaria Flavonoids Effectively Inhibit the Malignant Phenotypes of Non-small Cell Lung Cancer in an Id1-dependent Manner

Zhengxiao Zhao1, Baojun Liu1,2, Jing Sun1,2, Linwei Lu1,2, Lumei Liu1,2, Jian Qiu1,2, Qiuping Li1,2, Chen Yan1,2, Shan Jiang1,2, Nabijan Mohammadtursun1,2, Wenjuan Ma3, Mihui Li1,2, Jingcheng Dong1,✉, Weiyi Gong1,✉

1. Department of Integrative Medicine, Huashan Hospital, Fudan University, Shanghai, PR China
2. Institutes of Integrative Medicine, Fudan University, Shanghai, PR China
3. Department of dermatology, Huashan Hospital, Fudan University, Shanghai, PR China

Abstract

Non-small cell lung cancer (NSCLC) is the leading cause of cancer death in the world. Inhibitor of differentiation 1 (Id1) is overexpressed in NSCLC and involved in promoting its progression and metastasis. Identifying natural compounds targeting Id1 may have utility in NSCLC treatment. Here, we sought to determine whether the anti-tumor activities of Scutellaria flavonoids (SFs) were related to Id1. We reported that three SFs (baicalin, baicalein and wogonin) exhibited strong antitumor activity in NSCLC cells in vitro and in vivo. Id1 played a pivotal role on blockage of migration and invasion by SFs. Abrogation of invasion and migration mediated by baicalin, baicalein and wogonin were totally abolished by ectopic overexpression of Id1. Mechanistically, baicalin, baicalein and wogonin activated Rap1-GTP binding and dephosphorylated Akt and Src by suppressing a7nAChR, consequently triggering inhibition of Id1. Then attenuation of its downstream mediators, VEGF-A, N-cadherin, vimentin, combined with augment of E-cadherin led to the blockage of proliferation, EMT and angiogenesis of NSCLC. Overall, our data shed light on heretofore-undescribed role of SFs as modulators of Id1, which may be a useful strategy in the treatment of NSCLC.

Keywords: inhibitor of differentiation 1 (Id1), scutellaria flavonoids (SFs), non-small cell lung cancer (NSCLC), alpha 7 nicotinic acetylcholine receptor (α7nAChR)

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How to cite this article:
Zhao Z, Liu B, Sun J, Lu L, Liu L, Qiu J, Li Q, Yan C, Jiang S, Mohammadtursun N, Ma W, Li M, Dong J, Gong W. Scutellaria Flavonoids Effectively Inhibit the Malignant Phenotypes of Non-small Cell Lung Cancer in an Id1-dependent Manner. Int J Biol Sci 2019; 15(7):1500-1513. doi:10.7150/ijbs.33146. Available from http://www.ijbs.com/v15p1500.htm