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

Clinical & Translational Oncology : Official Publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico
J CaoD Chen

Abstract

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. 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. 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. Our findings clearly demonstrate the roles of eIF4E i...Continue Reading

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