IGFBP7 is associated to prognosis and could suppress cell survival in cholangiocarcinoma

Artif Cells Nanomed Biotechnol. 2018;46(sup2):817-825. doi: 10.1080/21691401.2018.1470524. Epub 2018 Jul 10.


Insulin-like growth factor-binding protein 7 (IGFBP7) is a secreted protein and its expression was restrained in varied solid tumours, but there was no report about biological role of IGFBP7 in cholangiocarcinoma (CCA). Here, we found that high expression of IGFBP7 correlated to a better overall survival in CCA patients. To investigate the hypothetic antineoplastic activity of IGFBP7 in CCA, we induced overexpression of IGFBP7 in QBC939 and RBE cells, as well as knockdown in HCCC9810 cells. And the biological functions triggered by level changes of IGFBP7 were assessed, including proliferation, cell cycle distribution, apoptosis and invasion evaluation. Cell growth assessment showed that enhanced IGFBP7 expression significantly retarded proliferation rates of QBC939 and RBE cells while an enhancement was observed in IGFBP7-inhibited HCCC9810 cells. The inhibition of cell viability was induced via G2/M phase arrest and apoptosis. Both QBC939 and RBE cells possess highly invasive ability, and IGFBP7 overexpression attenuated their serious invasiveness by reversing their mesenchymal phenotype to endothelial signature. We next investigated the potential mechanism involving in IGFBP7-induced tumour suppression and found that increased expression of IGFBP7 resulted in decrease of IGF-IR, IRS-1 and phosphor-AKT protein levels, accompanied with elevation of phorsphor-p38MAPK. These results suggest that IGFBP7 might be related to CCA carcinogenesis and metastasis, which further implicates that IGFBP7 might become a prospective benchmark for CCA diagnosis and therapy.

Keywords: Cholangiocarcinoma; cell viability; insulin-like growth factor-binding protein-7; invasion; p38 mitogen-activated protein kinase.

MeSH terms

  • Aged
  • Apoptosis
  • Bile Duct Neoplasms / diagnosis*
  • Bile Duct Neoplasms / genetics
  • Bile Duct Neoplasms / metabolism
  • Bile Duct Neoplasms / pathology*
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Cell Survival
  • Cholangiocarcinoma / diagnosis*
  • Cholangiocarcinoma / genetics
  • Cholangiocarcinoma / metabolism
  • Cholangiocarcinoma / pathology*
  • Epithelial-Mesenchymal Transition
  • Female
  • G2 Phase Cell Cycle Checkpoints
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Insulin-Like Growth Factor Binding Proteins / genetics
  • Insulin-Like Growth Factor Binding Proteins / metabolism*
  • M Phase Cell Cycle Checkpoints
  • Male
  • Middle Aged
  • Prognosis
  • Proto-Oncogene Proteins c-akt / metabolism
  • Signal Transduction
  • p38 Mitogen-Activated Protein Kinases / metabolism


  • Insulin-Like Growth Factor Binding Proteins
  • insulin-like growth factor binding protein-related protein 1
  • Proto-Oncogene Proteins c-akt
  • p38 Mitogen-Activated Protein Kinases