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Volatile oil from Saussurea lappa exerts antitumor efficacy by inhibiting epithelial growth factor receptor tyrosine kinase-mediated signaling pathway in hepatocellular carcinoma

Xuejing Lin, Zhangxiao Peng, Xiaohui Fu, Chunying Liu, Yang Xu, Weidan Ji, Jianhui Fan, Lei Chen, Lin Fang, Yao Huang and Changqing Su _

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Oncotarget. 2016; 7:79761-79773. https://doi.org/10.18632/oncotarget.12962

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Abstract

Xuejing Lin1,*, Zhangxiao Peng1,*, Xiaohui Fu2,*, Chunying Liu1, Yang Xu1, Weidan Ji1, Jianhui Fan1, Lei Chen1, Lin Fang3, Yao Huang2, Changqing Su1,3

1Department of Molecular Oncology, Eastern Hepatobiliary Surgical Hospital & National Center of Liver Cancer, Second Military Medical University, Shanghai 200438, China

2Department of Biliary Tract Surgery, Eastern Hepatobiliary Surgical Hospital, Second Military Medical University, Shanghai 200438, China

3Jiangsu Center for The Collaboration and Innovation of Cancer Biotherapy, Xuzhou Medical College, Xuzhou 221002, China

*These authors have contributed equally to this work

Correspondence to:

Changqing Su, email: [email protected]

Yao Huang, email: [email protected]

Keywords: VOSL, hepatocellular carcinoma, epithelial growth factor receptor, signaling, xenograft model

Received: June 20, 2016    Accepted: October 19, 2016    Published: October 28, 2016

ABSTRACT

Hepatocellular carcinoma (HCC) treatment remains lack of effective chemotherapeutic drugs, therefore, discovering novel anti-HCC drugs is a very attractive and urgent task. In this study, we reported VOSL (volatile oil from Saussurea lappa root) exhibits potent therapeutic effect on SMMC-7721 xenografts without obvious side effects. In the in vitro experiments, VOSL inhibited HCC cell proliferation by arresting cell cycle at S and G2/M phases, and induced HCC cell apoptosis by activating the Caspase3 pathway. VOSL also decreased the capability of HCC cell migration and invasion through MMP-9 depression. Moreover, mechanistic study indicated that VOSL can act as an epithelial growth factor receptor (EGFR) inhibitor to suppress EGFR activation and then to suppress its downstream MEK/P38 and PI3-K/Akt pathways. These results suggested that VOSL may be a novel anti-HCC drug candidate.


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