Oncotarget

Research Papers:

Apatinib inhibits VEGF signaling and promotes apoptosis in intrahepatic cholangiocarcinoma

Hong Peng _, Qiuyang Zhang, Jiali Li, Ning Zhang, Yunpeng Hua, Lixia Xu, Yubin Deng, Jiaming Lai, Zhenwei Peng, Baogang Peng, Minhu Chen, Sui Peng and Ming Kuang

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Oncotarget. 2016; 7:17220-17229. https://doi.org/10.18632/oncotarget.7948

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Abstract

Hong Peng1,*, Qiuyang Zhang2,*, Jiali Li1,*, Ning Zhang3, Yunpeng Hua1, Lixia Xu3, Yubin Deng4, Jiaming Lai5, Zhenwei Peng6, Baogang Peng1, Minhu Chen3, Sui Peng3, Ming Kuang1,7

1Department of Liver Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China

2Department of Internal Medicine, The University of Texas Southwestern Medical School, Dallas, Texas, USA

3Department of Gastroenterology and Hepatology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China

4Laboratory of Research Center for Translational Medicine, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China

5Department of Pancreato-Billary Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China

6Department of Oncology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China

7Department of Medical Ultrasound, Division of Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China

*These authors have contributed equally to this work.

Correspondence to:

Sui Peng, e-mail: pengsui@vip.163.com

Ming Kuang, e-mail: kuangminda@hotmail.com

Keywords: intrahepatic cholangiocarcinoma, VEGFR2, apatinib, apoptosis, PI3K

Received: October 18, 2015    Accepted: February 06, 2016    Published: March 07, 2016

ABSTRACT

Tumor cells co-express vascular endothelial growth factor (VEGF) and VEGF receptors (VEGFRs) that interact each other to support a self-sustainable cell growth. So far, this autocrine VEGF loop is not reported in human intrahepatic cholangiocarcinoma (ICC). Apatinib is a highly selective VEGFR2 inhibitor, but its effects on ICC have not been investigated. In this study, we reported that VEGF and phosphorylated VEGFR2 were expressed at a significantly high level in ICC patient tissues (P<0.05). In vitro, treating ICC cell lines RBE and SSP25 with recombinant human VEGF (rhVEGF) induced phosphorylation of VEGFR1 (pVEGFR1) and VEGFR2 (pVEGFR2); however, only the VEGFR2 played a role in the anti-apoptotic cell growth through activating a PI3K-AKT-mTOR anti-apoptotic signaling pathway which generated more VEGF to enter this autocrine loop. Apatinib inhibited the anti-apoptosis induced by VEGF signaling, and promoted cell death in vitro. In addition, Apatinib treatment delayed xenograft tumor growth in vivo. In conclusion, the autocrine VEGF/VEGFR2 signaling promotes ICC cell survival. Apatinib inhibits anti-apoptotic cell growth through suppressing the autocrine VEGF signaling, supporting a potential role for using Apatinib in the treatment of ICC.


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