Moreover, we revealed that cisplatin induced PTGS2 expression through the ROS-ERK1/2-NF-κB signaling axis, and PGE2 might strengthen PTGS2 expression through the PGE2-EPs-ERK1/2 positive feedback loop, which induced multidrug resistance of NSCLC cells via mediating the augmentation effects of cisplatin on BCL2 expression and the subsequent impairment of cell apoptosis. The gene discussed is BCL2; the disease is non-small cell lung carcinoma.