Induction Of Apoptosis With TRAIL And Chemotherapeutic Drugs In Non-small-cell Lung Cancer

Objective: The aim of this study was to investigate whether TNF-related apoptosis-inducing ligand (TRAIL) alone or in combination with chemotherapeutic drugs could induce apoptosis in Non-small-cell lung cancer cells,Methods: Non-small-cell lung cell line NC1-H460 was treated with TRAIL in serial concentrations from 20~160ng/ml alone, with a fixed dose of each chemotherapeutic drug (Doxorubicin, Cisplatin, Paclitaxel) alone or the combination of TRAIL and each drug. Caspase 3 activation was measured after 8 hours of the treatment. Morphological changes of the nuclei were investigated using Fluorescence microscope and the sub G1 fraction of the cells were determined with FCM.Results: TRAIL resulted in a dose-dependent increase in Caspase 3 activity especially when combined with chemotherapeutic drugs. Karyorrhexis was found in both TRAIL and drug treated groups and was most notably seen in the combination groups. The percentage of apoptotic cells increased significantly upon the combined treatment of TRAIL and chemotherapeutic drugs than in the groups with individual treatment.Conclusion: The data suggest that TRAIL is a potent inducer of apoptosis in the NSCLC cell line NC1-H460. The combination of TRAIL and chemotherapeutic drugs greatly enhance their pro-apoptotic effect in a synergistic manner, which could be a novel way to overcome chemoresistance in the clinical setting.