title: eIF5A2 is an alternative pathway for cell proliferation in cetuximab-treated epithelial hepatocellular carcinoma.
abstract: Heaptocellular carcinoma (HCC) is still a great health problem around the world. Recently, the cetuximab has been implicated to have therapeutic values for HCC. However, cetuximab-resistance has also been synchronously reported pertaining to HCC treatment. This study aimed to evaluate the role of eIF5A2 in cetuximab-treated HCC cell proliferation, and whether eIF5A2 specific inhibitor GC7 has any effects on cetuximab-mediated proliferation inhibition in HCC cell lines. It was observed that GC7 significantly inhibited cell proliferation in HCC cell lines. GC7 synergized cetuximab to inhibit the proliferation in epithelial HCC cell lines HepG2, Huh7 and Hep3B, but not in mesenchymal cell lines SNU387 and SNU449. Knockdown of eIF5A-2 by specific siRNA exhibited the similar effects as GC7 did. In cetuximab-treated cells, cetuximab decreased the protein level of EGFR and phosphorylated STAT3 and unexpectedly up-regulated the expression level of eIF5A2, indicating the activation of eIF5A2 pathway. In turn, cetuximab also synergized GC7 to inhibit cell proliferation in epithelial cell lines. GC7 also suppressed hypoxia-induced cell proliferation in epithelial cell lines. These data suggest that eIF5A2 is an alternative pathway for cell proliferation in epithelial HCC cells escaping from the cytotoxicity of cetuximab. The eIF5A inhibitor GC7 might be a potent agent that promotes the cytotoxicity of cetuximab on epithelial HCC cells.
authors.affiliation: Department of Hepatobiliary and Pancreatic Surgery, Henan Provincial People's Hospital, Zhengzhou University People's Hospital Zhengzhou, PR China.
authors.forename: Fei
authors.initials: F
authors.lastname: Xue
authors.affiliation: Department of Hepatobiliary and Pancreatic Surgery, Henan Provincial People's Hospital, Zhengzhou University People's Hospital Zhengzhou, PR China.
authors.forename: Yanhui
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Hepatobiliary and Pancreatic Surgery, Henan Provincial People's Hospital, Zhengzhou University People's Hospital Zhengzhou, PR China.
authors.forename: Haoyuan
authors.initials: H
authors.lastname: Chu
authors.affiliation: Department of Hepatobiliary and Pancreatic Surgery, Henan Provincial People's Hospital, Zhengzhou University People's Hospital Zhengzhou, PR China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Wen
authors.affiliation: Department of Hepatobiliary and Pancreatic Surgery, Henan Provincial People's Hospital, Zhengzhou University People's Hospital Zhengzhou, PR China.
authors.forename: Lei
authors.initials: L
authors.lastname: Yan
authors.affiliation: Department of Hepatobiliary and Pancreatic Surgery, Henan Provincial People's Hospital, Zhengzhou University People's Hospital Zhengzhou, PR China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Tang
authors.affiliation: Department of Hepatobiliary and Pancreatic Surgery, Henan Provincial People's Hospital, Zhengzhou University People's Hospital Zhengzhou, PR China.
authors.forename: Erhui
authors.initials: E
authors.lastname: Xiao
authors.affiliation: Department of Hepatobiliary and Pancreatic Surgery, Henan Provincial People's Hospital, Zhengzhou University People's Hospital Zhengzhou, PR China.
authors.forename: Dongyi
authors.initials: D
authors.lastname: Zhang
authors.affiliation: Department of Hepatobiliary and Pancreatic Surgery, Henan Provincial People's Hospital, Zhengzhou University People's Hospital Zhengzhou, PR China.
authors.forename: Hongwei
authors.initials: H
authors.lastname: Zhang
keywords: Cetuximab; GC7; eIF5A; hepatocellular carcinoma