Regulation of proliferation and invasion by the IGF signalling pathway in Epstein-Barr virus-positive gastric cancer

Inhye Jeong, Sun Kyoung Kang, Woo Sun Kwon, Hyun Jeong Kim, Kyoo Hyun Kim, Hyun Myong Kim, Andre Lee, Suk Kyeong Lee, Thomas Bogenrieder, Hyun Cheol Chung, Sun Young Rha

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5 Citations (Scopus)


Several carcinomas including gastric cancer have been reported to contain Epstein-Barr virus (EBV) infection. EBV-associated gastric cancer (EBVaGC) is classified as one of four molecular subtypes of gastric cancer by The Cancer Genome Atlas (TCGA) group with increased immune-related signatures. Identification of EBV-dependent pathways with significant biological roles is needed for EBVaGC. To compare the biological changes between AGS gastric epithelial cells and EBV-infected AGS (AGS-EBV) cells, proliferation assay, CCK-8 assay, invasion assay, cell cycle analysis, RT-PCR, Western blot and ELISA were performed. BI836845, a humanized insulin-like growth factor (IGF) ligand-neutralizing antibody, was used for IGF-related signalling pathway inhibition. AGS-EBV cells showed slower proliferating rate and higher sensitivity to BI836845 compared to AGS cells. Moreover, invasiveness of AGS-EBV was increased than that of AGS, and BI836845 treatment significantly decreased the invasiveness of AGS-EBV. Although no apoptosis was detected, entry into the S phase of the cell cycle was delayed in BI836845-treated AGS-EBV cells. In conclusion, AGS-EBV cells seem to modulate their proliferation and invasion through the IGF signalling pathway. Inhibition of the IGF signalling pathway therefore could be a potential therapeutic strategy for EBVaGC.

Original languageEnglish
Pages (from-to)5899-5908
Number of pages10
JournalJournal of Cellular and Molecular Medicine
Issue number12
Publication statusPublished - 2018 Dec

Bibliographical note

Publisher Copyright:
© 2018 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Cell Biology


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