Erlotinib Activates Different Cell Death Pathways in EGFR-mutant Lung Cancer Cells Grown in 3D <i>Versus</i> 2D Culture Systems

Background/Aim: Non-small cell lung cancer patients with epidermal growth factor receptor (EGFR) mutation have been shown to a good response erlotinib, tyrosine kinase inhibitor of EGFR. In this study, we found that the death pathways activated by erlotinib in 2D and 3D culture systems are different. Materials Methods: The induced were evaluated flow cytometry immunoblotting both EGFR mutant cells. Results: Treatment caspase 8 activation up-regulation TNF-related apoptosis-inducing ligand (TRAIL) expression only cultures. Knockdown TRAIL attenuated erlotinib-induced caspase-8 apoptosis Erlotinib also increased LC3, an autophagy marker, c-Jun N terminal (JNK) activation. Both 3-MA as SP600125 JNK inhibitor, significantly inhibited death. Conclusion: induces apoptotic cultures through autophagy-TRAIL-JNK pathway.