Inhibition of mTOR restores cisplatin sensitivity through down-regulation of growth and anti-apoptot
July 3rd, 2008 | by admin |Inhibition of mTOR restores cisplatin sensitivity through down-regulation of growth and anti-apoptotic proteins.
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. Importantly, 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. However, continuous exposure to CCI-779 leads to expression of P-gp1 (P-glycoprotein1) and should be taken into consideration in designing clinical trials.
Wangpaichitr M, Wu C, You M, Kuo MT, Feun L, Lampidis T, Savaraj N.
Department of Molecular Cell and Developmental Biology, University of Miami School of Medicine, Miami, FL, USA.