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

J Cao1, X Sun1, X Zhang1

  • 1Department of Urology, Xiangyang Central Hospital, Hospital Affiliated to Hubei University of Arts and Science, 39 Jingzhou Street, Xiangyang, 441021, Hubei, People's Republic of China.

Clinical & Translational Oncology : Official Publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico
|November 1, 2017
PubMed
Abstract

Insights

Inhibition of eukaryotic translation initiation factor 4E (eIF4E) hinders renal cell carcinoma (RCC) growth and metastasis. Targeting eIF4E with ribavirin sensitizes RCC to chemotherapy and immunotherapy, supporting clinical trials.

Area of Science:

  • Oncology
  • Molecular Biology
  • Translational Research

Background:

  • Overexpression of eukaryotic translation initiation factor 4E (eIF4E) is linked to poor prognosis in renal cell carcinoma (RCC).
  • The specific roles of eIF4E in RCC progression and treatment resistance remain largely unexplored.

Purpose of the Study:

  • To investigate the functional significance of eIF4E in renal cell carcinoma (RCC).
  • To evaluate the therapeutic potential of inhibiting eIF4E in RCC treatment.

Main Methods:

  • Utilized a pharmacological inhibitor (ribavirin) and genetic knockdown (siRNA) to inhibit eIF4E in RCC cell lines.
  • Assessed the impact of eIF4E inhibition on RCC cell proliferation, migration, apoptosis, and response to chemo-/immunotherapy in vitro and in vivo.

Main Results:

  • eIF4E inhibition by ribavirin or siRNA significantly reduced RCC cell proliferation and migration while inducing apoptosis.
  • Inhibition of eIF4E suppressed eIF4E-regulated protein translation and activity in RCC cells.
  • eIF4E inhibition markedly enhanced the sensitivity of RCC cells to conventional chemo- and immunotherapeutic agents.

Conclusions:

  • eIF4E plays a critical role in the growth, survival, metastasis, and therapeutic resistance of renal cell carcinoma (RCC).
  • Ribavirin demonstrates preclinical efficacy in inhibiting RCC progression and sensitizing tumors to other therapies.
  • These findings provide a strong rationale for clinical trials combining ribavirin with chemo-/immunotherapy for RCC treatment.
Keywords:
Protein translationRCCRibavirineIF4E

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