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Targeting eIF4E signaling with ribavirin as a sensitizing strategy for ovarian cancer

Jing Jin1, Wei Xiang2, Shuang Wu3

  • 1The First Clinical College, Hubei University of Chinese Medicine, Wuhan, Hubei, China.

Biochemical and Biophysical Research Communications
|February 12, 2019
PubMed

Insights

Ribavirin, an antiviral drug, effectively inhibits ovarian cancer growth by targeting eukaryotic translation initiation factor 4E (eIF4E). This drug shows promise when combined with cisplatin, especially in cancers dependent on eIF4E.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Eukaryotic translation initiation factor 4E (eIF4E) plays a crucial role in various cancers, including ovarian cancer.
  • Targeting eIF4E presents a potential therapeutic strategy for ovarian cancer treatment.

Purpose of the Study:

  • To investigate the efficacy of ribavirin, an FDA-approved antiviral drug, in inhibiting eIF4E in ovarian cancer.
  • To explore the underlying mechanisms of ribavirin's action and its potential as a combination therapy with cisplatin.

Main Methods:

  • Treatment of multiple ovarian cancer cell lines with ribavirin at clinically relevant doses.
  • Analysis of signaling pathways, including Akt/mTOR and eIF4E/p70S6K.
  • In vitro and in vivo studies using cell cultures and xenograft mouse models.
  • Assessment of ribavirin's efficacy in combination with cisplatin.

Main Results:

  • Ribavirin significantly inhibits ovarian cancer cell growth and survival across different subtypes.
  • Ribavirin suppresses Akt/mTOR and eIF4E/p70S6K signaling pathways, with eIF4E phosphorylation at S209 being critical.
  • Combination therapy with ribavirin and cisplatin demonstrates superior efficacy compared to cisplatin alone.
  • Ovarian cancer cell sensitivity to ribavirin correlates with eIF4E expression levels, which are elevated in tumor tissues.

Conclusions:

  • Ribavirin is an effective inhibitor of eIF4E in ovarian cancer, regardless of subtype.
  • Ribavirin shows potential as an adjuvant therapy for ovarian cancer, particularly in eIF4E-dependent cases.
  • Differential eIF4E expression in ovarian tumors suggests potential for personalized treatment strategies.
Keywords:
Akt/mTORDrug combinationOvarian cancerRibavirineIF4E

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