synergistic effect of subtoxic-dose cisplatin and trail to mediate apoptosis by down-regulating decoy receptor 2 and up-regulating caspase-8, caspase-9 and bax expression on nci-h460 and a549 cells

objective(s): although tumor necrosis factor-related apoptosis-inducing ligand (trail) can selectively induce apoptosis in tumor cells, more than half of tumors including non-small cell lung cancer (nsclc) exhibit trail-resistance. the purpose of this study was to determine whether subtoxic-dose cisplatin and trail could synergistically enhance apoptosis on nsclc cells and investigate its underlying mechanisms. materials and methods:nci-h460 and a549 cells were treated with trail alone, cisplatin alone or combination treatment in this study. the cytotoxicity was evaluated according to sulforhodamine b assay, and apoptosis was examined using hoechst 33342 staining and flow cytometry. the mrna and protein levels of trail receptors and apoptotic proteins including caspase-8, caspase-9, bcl-2 and bax were determined by rt-pcr and western blotting, respectively. results:our results showed that nci-h460 cells were sensitive to trail, whereas a549 cells were resistant. however, subtoxic-dose cisplatin could enhance the both cells to trail-mediated cell proliferation inhibition and apoptosis. the underlying mechanisms might be associated with the down-regulation of dcr2 and up-regulation of caspase-8, caspase-9 and bax. conclusion:subtoxic-dose cisplatin could enhance both trail- sensitive and trail- resistant nsclc cells to trail-mediated apoptosis. these findings motivated further studies to evaluate such a combinatory therapeutic strategy against nsclc in the animal models.