Apatinib inhibits VEGF signaling and promotes apoptosis in intrahepatic cholangiocarcinoma

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 inhi...

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Main Authors:	Peng, Hong, Zhang, Qiuyang, Li, Jiali, Zhang, Ning, Hua, Yunpeng, Xu, Lixia, Deng, Yubin, Lai, Jiaming, Peng, Zhenwei, Peng, Baogang, Chen, Minhu, Peng, Sui, Kuang, Ming
Format:	Online
Language:	English
Published:	Impact Journals LLC 2016
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4941382/

id	pubmed-4941382
recordtype	oai_dc
spelling	pubmed-49413822016-07-19 Apatinib inhibits VEGF signaling and promotes apoptosis in intrahepatic cholangiocarcinoma Peng, Hong Zhang, Qiuyang Li, Jiali Zhang, Ning Hua, Yunpeng Xu, Lixia Deng, Yubin Lai, Jiaming Peng, Zhenwei Peng, Baogang Chen, Minhu Peng, Sui Kuang, Ming Research Paper 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. Impact Journals LLC 2016-03-07 /pmc/articles/PMC4941382/ /pubmed/26967384 http://dx.doi.org/10.18632/oncotarget.7948 Text en Copyright: © 2016 Peng et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Peng, Hong Zhang, Qiuyang Li, Jiali Zhang, Ning Hua, Yunpeng Xu, Lixia Deng, Yubin Lai, Jiaming Peng, Zhenwei Peng, Baogang Chen, Minhu Peng, Sui Kuang, Ming
spellingShingle	Peng, Hong Zhang, Qiuyang Li, Jiali Zhang, Ning Hua, Yunpeng Xu, Lixia Deng, Yubin Lai, Jiaming Peng, Zhenwei Peng, Baogang Chen, Minhu Peng, Sui Kuang, Ming Apatinib inhibits VEGF signaling and promotes apoptosis in intrahepatic cholangiocarcinoma
author_facet	Peng, Hong Zhang, Qiuyang Li, Jiali Zhang, Ning Hua, Yunpeng Xu, Lixia Deng, Yubin Lai, Jiaming Peng, Zhenwei Peng, Baogang Chen, Minhu Peng, Sui Kuang, Ming
author_sort	Peng, Hong
title	Apatinib inhibits VEGF signaling and promotes apoptosis in intrahepatic cholangiocarcinoma
title_short	Apatinib inhibits VEGF signaling and promotes apoptosis in intrahepatic cholangiocarcinoma
title_full	Apatinib inhibits VEGF signaling and promotes apoptosis in intrahepatic cholangiocarcinoma
title_fullStr	Apatinib inhibits VEGF signaling and promotes apoptosis in intrahepatic cholangiocarcinoma
title_full_unstemmed	Apatinib inhibits VEGF signaling and promotes apoptosis in intrahepatic cholangiocarcinoma
title_sort	apatinib inhibits vegf signaling and promotes apoptosis in intrahepatic cholangiocarcinoma
description	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.
publisher	Impact Journals LLC
publishDate	2016
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4941382/
_version_	1613607717277007872

Apatinib inhibits VEGF signaling and promotes apoptosis in intrahepatic cholangiocarcinoma

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