Oncotarget

Research Papers:

Deguelin suppresses angiogenesis in human hepatocellular carcinoma by targeting HGF-c-Met pathway

Ming Li, Xinfang Yu, Wei Li, Ting Liu, Gang Deng, Wenbin Liu, Haidan Liu _ and Feng Gao

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Oncotarget. 2018; 9:152-166. https://doi.org/10.18632/oncotarget.22077

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Abstract

Ming Li4,5,*, Xinfang Yu6,*, Wei Li7,*, Ting Liu1, Gang Deng8, Wenbin Liu9, Haidan Liu3 and Feng Gao1,2

1Department of Ultrasonography, The Third Xiangya Hospital of Central South University, Changsha, Hunan 410013, P.R. China

2State Key Laboratory of Powder Metallurgy, Central South University, Changsha, Hunan 410006, P.R. China

3Clinical Center for Gene Diagnosis and Therapy, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410011, P.R. China

4School of Stomatology, Hunan University of Chinese Medicine, Changsha, Hunan 410208, P.R. China

5Changsha Stomatological Hospital, Changsha, Hunan 410004, P.R. China

6Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio 44195, USA

7Department of Radiology, The Third Xiangya Hospital of Central South University, Changsha, Hunan 410013, P.R. China

8Department of Hepatobiliary and Pancreatic Surgery, The Third Xiangya Hospital of Central South University, Changsha, Hunan 410013, P.R. China

9Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan 410013, P.R. China

*These authors contributed equally to this work

Correspondence to:

Haidan Liu, email: [email protected]

Feng Gao, email: [email protected]

Keywords: hepatocellular carcinoma; deguelin; angiogenesis; VEGF; c-Met

Received: July 20, 2016     Accepted: October 11, 2017     Published: October 26, 2017

ABSTRACT

Angiogenesis plays a crucial role in the development of human hepatocellular carcinoma (HCC). In the present study, we found a natural compound, deguelin, has a profound anti-angiogenesis effect on HCC. Deguelin suppressed vascular endothelial growth factor (VEGF)-induced human umbilical vascular endothelial cells (HUVECs) proliferation, migration, invasion, and capillary-like tube formation in vitro and reduced tumor angiogenesis in vivo. We discovered that VEGF receptor-mediated signal transduction cascades in HUVECs were inhibited by deguelin. Deguelin decreased the autocrine of VEGF in HCC cells in a time- and dose-dependent manner. Additionally, deguelin suppressed HGF-induced activation of the c-Met signaling pathway. Knocking down c-Met or inhibition of c-Met activation impaired HGF-mediated VEGF production. Importantly, we produced patient-derived hepatocellular carcinoma xenografts to evaluate the therapeutic effect of deguelin in vivo. Taken together, these results indicate that deguelin could inhibit HCC through suppression of angiogenesis on vascular endothelial cells and reduction of proangiogenic factors in cancer cells.


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