Baicalein Inhibits Orthotopic Human Non-Small Cell Lung Cancer Xenografts via Src/Id1 Pathway.

Zhengxiao Zhao,Lumei Liu,Jian Qiu,Weiyi Gong,Qiuping Li,Jingcheng Dong,Nabijan Mohammadtursun,Shan Jiang,Jing Sun,Baojun Liu,Linwei Lu,Chen Yan,Mihui Li,Wenjuan Ma

doi:10.1155/2019/9806062

Abstract

Non-small cell lung cancer (NSCLC) is one of the most lethal cancers worldwide. Inhibitor of differentiation 1 (Id1) is the member mostly linked to tumorigenesis in Id family and a potential molecular target in cancer therapy. In the current study, we established an orthotopic lung cancer model by injecting athymic nude mice with A549 cells and evaluated the antitumor effect of baicalein and expression of Id1-related proteins in vivo and in vitro. Micro-CT images showed that tumor volume in baicalein group was significantly reduced. Western blot analysis revealed that baicalein suppressed the expression of Id1 protein, epithelial-to-mesenchymal transition (EMT) related molecules (N-Cadherin, vimentin), and angiogenesis related protein (VEGF-A), accompanied by upregulation of epithelial markers (such as E-cadherin). In addition, phosphorylation of upstream molecular Src was significantly restrained after baicalein treatment. This study firstly demonstrates that baicalein inhibits tumor growth in orthotopic human NSCLC xenografts via targeting Src/Id1 pathway.

Highlights

Lung cancer is currently the leading cause of cancer-related mortality worldwide, with more than 1.3 million deaths each year [1]
We established an orthotopic lung cancer model through a visible transthoracic injection with A549 cells and demonstrated that baicalein was effective in this model
We identified inhibitor of differentiation 1 (Id1) as the pivotal respondent to baicalein in its anti-tumor effect

Summary

Introduction

Lung cancer is currently the leading cause of cancer-related mortality worldwide, with more than 1.3 million deaths each year [1]. Many new systemic therapies for treating lung cancer have been developed in recent years, the prognosis has little improvement in the past decades. Id1 has been shown to be expressed in a variety of tissue microarray samples in non-small cell lung cancer (NSCLC) [6]. Genetic loss of Id1 in the host tissue increased survival and impaired liver colonization of Id -/- lung cancer mice [10]. These studies suggest that therapeutic targeting of Id1 is an attractive strategy for combating lung cancer

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Conclusion