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, Ming Kuang

Research output: Contribution to journalArticle

68 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)17220-17229
Number of pages10
JournalOncotarget
Volume7
Issue number13
DOIs
StatePublished - Mar 29 2016

Keywords

  • Apatinib
  • Apoptosis
  • Intrahepatic cholangiocarcinoma
  • PI3K
  • VEGFR2

ASJC Scopus subject areas

  • Oncology

Fingerprint Dive into the research topics of 'Apatinib inhibits VEGF signaling and promotes apoptosis in intrahepatic cholangiocarcinoma'. Together they form a unique fingerprint.

  • Cite this

    Peng, H., Zhang, Q., Li, J., Zhang, N., Hua, Y., Xu, L., Deng, Y., Lai, J., Peng, Z., Peng, B., Chen, M., Peng, S., & Kuang, M. (2016). Apatinib inhibits VEGF signaling and promotes apoptosis in intrahepatic cholangiocarcinoma. Oncotarget, 7(13), 17220-17229. https://doi.org/10.18632/oncotarget.7948