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Clinical and Translational Oncology

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01-06-2018 | Research Article

Inhibition of eIF4E cooperates with chemotherapy and immunotherapy in renal cell carcinoma

Authors: J. Cao, X. Sun, X. Zhang, D. Chen

Published in: Clinical and Translational Oncology | Issue 6/2018

Abstract

Purpose

Although overexpression of the eukaryotic translation initiation factor 4E (eIF4E) is detected in patients with renal cell carcinoma (RCC) and associated with poor prognosis, the possible roles of eIF4E in RCC have not been revealed.

Methods

The effects of eIF4E inhibition on cell growth, migration, survival, chemo-/immunotherapy and eIF4E pathways via pharmacological inhibitor and genetic siRNA knockdown were analyzed in RCC cells.

Results

In this work, we demonstrate that eIF4E is critically involved in multiple biological functions of RCC. We firstly inhibited eIF4E activity by ribavirin in two cell lines (Caki-1 and ACHN) representing RCC metastasis models. We demonstrated that ribavirin inhibited proliferation and migration and induced apoptosis in RCC in a dose-dependent manner. We further confirmed that the inhibitory effects of ribavirin were attributed to its ability in inhibiting eIF4E-regulated protein translation and activity. eIF4E inhibition using siRNA knockdown mimicked ribavirin’s effector in RCC cells. Importantly, eIF4E inhibition by both ribavirin and siRNA knockdown significantly sensitized RCC response to chemo- and immunotherapeutic agents in vitro as well as in vivo.

Conclusions

Our findings clearly demonstrate the roles of eIF4E in RCC growth, survival, metastasis and resistance. Ribavirin is an antiviral drug, and its clinical efficacy is currently being investigated in the treatment of various cancers. Our findings support and provide a preclinical evidence for clinical trial for the combination of ribavirin with chemo-/immunotherapy in RCC.

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Title: Inhibition of eIF4E cooperates with chemotherapy and immunotherapy in renal cell carcinoma
Authors: J. Cao
X. Sun
X. Zhang
D. Chen
Publication date: 01-06-2018
Publisher: Springer International Publishing
Published in: Clinical and Translational Oncology / Issue 6/2018
Print ISSN: 1699-048X
Electronic ISSN: 1699-3055
DOI: https://doi.org/10.1007/s12094-017-1786-z

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Abstract

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