RT Journal Article
SR Electronic
T1 mTOR inhibition blocks tumor growth and pleural fluid accumulation in experimental murine mesothelioma
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP 2947
VO 38
IS Suppl 55
A1 Marialena Vazakidou
A1 Sophia Magouta
A1 Charis Moschos
A1 Magda Stratiki
A1 Charis Roussos
A1 Ioannis Kalomenidis
YR 2011
UL http://erj.ersjournals.com/content/38/Suppl_55/2947.abstract
AB mTOR is up-regulated in malignant mesothelioma. We aimed to evaluate the effect of Temsirolimus, an mTOR inhibitor, in in vivo models of the disease.AE17 and AB1 murine mesothelioma cells were injected into the right flank of syngeneic mice (C57BL/6 and BALB-c, respectively) to create subcutaneous tumors. C57BL/6 mice were injected intrapleurally with AE17 cells to create pleural tumors and effusions. Animals were treated with Temsirolimus (20mg/kg) or vehicle, 5 days/week starting when tumors become palpable (flank model) or on days 2-6, 9-15 following the intrapleural injection of tumor cells (pleural model).Among mice with AE17 flank tumors, the mean ±SEM tumor volume at day 26 was 1261±383mm3 in control and 383±86mm3 in treated animals (p<0.001). Tumor cell apoptosis, assessed by TUNEL was significantly enhanced in mice treated with Temsirolimus (p<0.001). In the AB1 flank model, tumor volume was 1197±253mm3 in control and 174±76 mm3 in treated animals (p=0.026). Among mice with pleural AE17 tumors, the mean ±SEM pleural fluid volume at day 15 was 532±119microL in control and 240±44microL in treated animals (p=0.018). The mean ±SEM pleural tumor weight was 739±72mg in control and 256±10mg in treated animals (p<0.001). Additionally, Temsirolimus retarded murine mesothelioma cell growth and reduce the phosphorylation/activation of the mTOR downstream protein, p70S6K protein, in vitro.Inhibition of mTOR substantially reduced syngeneic mesothelioma growth blocked pleural fluid accumulation in animals bearing mesothelioma tumors.