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Silencing the expression of copine-III enhances the sensitivity of hepatocellular carcinoma cells to the molecular targeted agent sorafenib

Authors Chen Z, Jiang ZK, Zhang WZ, He BX

Received 9 March 2018

Accepted for publication 15 May 2018

Published 29 August 2018 Volume 2018:10 Pages 3057—3067

DOI https://doi.org/10.2147/CMAR.S167781

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Amy Norman

Peer reviewer comments 2

Editor who approved publication: Dr Leylah Drusbosky


Zhuo Chen, Zhengkui Jiang, Wenzhou Zhang, Baoxia He

The Affiliated Cancer Hospital of Zhengzhou University/Henan Cancer Hospital, Zhengzhou 450008, People’s Republic of China

Background: The application of the oral targeted therapeutic agent sorafenib provides new hope for patients suffering from advanced stages of hepatocellular carcinoma (HCC), but the prognosis of such patients remains poor due to the rapid development of the multidrug resistance process in cancer pathogenesis. The present work evaluated whether copine-III, a novel cancer regulator encoded by the CPNE3 gene, would be a potential indicator of sorafenib resistance in HCC treatment.
Materials and methods: The endogenous expression of copine-III in clinical specimens was examined by quantitative polymerase chain reaction. Copine-III siRNA was transfected into HCC cells to downregulate copine-III expression. The effect of copine-III on sorafenib’s antitumor activation was identified by in vitro and in vivo experiments (MTT, Transwell, and flow cytometry as well as a nude mice model).
Results: High levels of copine-III in clinical specimens are related to poor prognosis of advanced HCC patients on sorafenib treatment. Infection of Ad-siCPNE3 significantly decreased the endogenous expression of copine-III and enhanced the susceptibility of MHCC97-H cells to sorafenib: the IC50 value decreased from 1.15±0.11 to 0.25±0.05 μmol/L. Moreover, silencing copine-III enhanced the effect of sorafenib on apoptosis, in vitro invasion/migration, and subcutaneous or intrahepatic growth of MHCC97-H cells in nude mice.
Conclusion: Copine-III is a novel potential indicator of prognosis for patients who received sorafenib for advanced HCC treatment.

Keywords: hepatocellular carcinoma, CPNE3, copine-III, molecular targeted agent, sorafenib-resistance

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