Human mesothelioma cells exhibit tumor cell-specific differences in phosphatidylinositol 3-kinase/AKT activity that predict the efficacy of Onconase

Maria E. Ramos-Nino, Giovina Vianale, Tara Sabo-Attwood, Luciano Mutti, Camilo Porta, Nicholas Heintz, Brooke T. Mossman

Research output: Contribution to journalArticlepeer-review

Abstract

Malignant mesothelioma is an aggressive cancer with no known cure, which has become a therapeutic challenge. Onconase is one of few chemotherapeutic agents that have been studied in patients with malignant mesothelioma that has the advantage of low toxicity and limited side effects. Here, we evaluate the effect of Onconase on killing of malignant mesothelioma cells and how the phosphatidylinositol 3-kinase/AKT (PI3-K/AKT) survival pathway influences this effect. Our results show that Onconase induces apoptosis in malignant mesothelioma cell lines and that this effect is tumor cell specific. Malignant mesothelioma cell lines with the highest AKT activation, which correlated with the presence of the SV40 large and small T antigen (SV40 +), were the most resistant to the drug. Finally, a cooperative effect was observed between small molecule inhibitors of PI3-K and Onconase in the killing of malignant mesothelioma cells. Our results suggest that kinase screening of individual malignant mesotheliomas for endogenous levels of activated PI3-K/AKT may be predictive of the efficacy of Onconase and possibly other chemotherapeutic agents.

Original languageEnglish
Pages (from-to)835-842
Number of pages8
JournalMolecular Cancer Therapeutics
Volume4
Issue number5
DOIs
Publication statusPublished - May 2005

ASJC Scopus subject areas

  • Oncology
  • Drug Discovery
  • Pharmacology

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