Oxaliplatin sensitizes OS cells to TRAIL-induced apoptosis via down-regulation of Mcl1.

PURPOSE To investigate the killing effect on OS cells of a combination of oxaliplatin and TRAIL and related molecular mechanisms. METHODS TRAIL and oxaliplatin were applied to OS732 cells singly or jointly and survival inhibition rates were measured by MTT assay, changes of cellular shape being assessed with inverted phase contrast and fluorescence microscopy. Apoptotic rates were analyzed by flow cytometry (FCM) and immunocytochemistry was used to examine Mcl1 expression of OS732 cells. RESULTS The survival inhibition rate of combined application of 100 μg/ml TRAIL and 1 μg/ml oxaliplatin on OS-732 cells was significantly higher than that of either agent singly (p<0.01). Changes of cellular shape and apoptotic rates also indicated apoptosis-inducing effects of combined application to be much stronger than those of individual application. Oxaliplatin had the effect of down-regulating Mcl1 expression and sensitizing OS cells to TRAIL-induced apoptosis. CONCLUSION A combination of TRAIL and oxaliplatin exerts strong killing effects on OS-732 cells which might be related to down-regulation of Mcl1 expression.