Icotinib inhibits the proliferation of hepatocellular carcinoma cells in vitro and in vivo dependently on EGFR activation and PDL1 expression
Authors Sun J, Jiang W, Tian D, Guo Q, Shen Z
Received 11 July 2018
Accepted for publication 18 October 2018
Published 21 November 2018 Volume 2018:11 Pages 8227—8237
Checked for plagiarism Yes
Review by Single-blind
Peer reviewers approved by Dr Andrew Yee
Peer reviewer comments 2
Editor who approved publication: Dr Leo Jen-Liang Su
Jisan Sun, Wentao Jiang, Dazhi Tian, Qingjun Guo, Zhongyang Shen
Department of Liver Transplantation, Tianjin First Center Hospital, First Clinical Institute of Tianjin Medical University, Nan Kai District, Tianjin 300192, People’s Republic of China
Purpose: Hepatocellular carcinoma (HCC) accounts for one of the most prevalent tumor types in the world and still lacks an effective treatment regimen. The EGFR tyrosine-kinase inhibitor icotinib is capable of inhibiting proliferation of several kinds of cancer cells, but its anticancer effect in HCC is still not verified.
Methods: In the current study, ten HCC cell lines were selected to test their original EGFR-activation status and PDL1 protein level, and in vitro antiproliferation assays were also conducted to analyze the IC50 and further investigate the correlation between IC50 and protein level of phosphorylated EGFR and PDL1. A in vivo nude mouse xenograft animal model was used as well to analyze its anticancer effect.
Results: Icotinib showed significant inhibitory effects only on HCC cell lines that had both higher p-EGFR and PDL1 protein level. This specific HCC cell line was subcutaneously injected to establish the in vivo xenograft tumor model, and icotinib reduced tumor weight remarkably and growth dose dependently. Molecular mechanism study revealed that icotinib inhibited the phosphorylation of EGFR and PDL1 expression in cancer cells and activated apoptosis. Knocking down PDL1 significantly reduced the inhibitory effect of icotinib on HCC, and knocking in PDL1 increased the sensitivity of icotinib in HCC.
Conclusion: The current research suggests that icotinib has an inhibitory effect on a subgroup of HCC cells that have both higher p-EGFR and PDL1. This hints at the potential clinical usage of icotinib in HCC based on PDL1-biomarker examination.
Keywords: hepatocellular carcinoma, epidermal growth factor receptor, icotinib, PDL1 protein
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