Inhibition of mTOR restores cisplatin sensitivity through down-regulation of growth and anti-apoptotic proteins

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59 Scopus citations

Abstract

We show that cisplatin resistance in certain lung cancer cell lines can be reversed through inhibition of mTOR (mammalian Target of Rapamycin). These cell lines appear to possess high levels of phospho-mTOR, phospho-AKT and other growth-related proteins, such as hTERT (human telomerase reverse transcriptase), and Cyclin D3 which decrease upon inhibition of mTOR. Interestingly in one cisplatin resistant cell line which expresses BCL2/BCLxL, treatment with mTOR inhibitor (CCI-779) results in decreased levels of these anti-apoptotic proteins and may contribute to increasing apoptosis. Moreover, continuous exposure to CCI-779 was found to increase the expression of the multi-drug resistant P-gp1(P-gycoprotein1) efflux pump and therefore should be taken into consideration when designing clinical trials with this compound.

Original languageEnglish (US)
Pages (from-to)124-127
Number of pages4
JournalEuropean Journal of Pharmacology
Volume591
Issue number1-3
DOIs
StatePublished - Sep 4 2008

Keywords

  • BCL2
  • BCLxL
  • Cisplatin resistance
  • Lung cancer
  • mTOR

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Pharmacology

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