Figure 8. The hypothetical mechanism underlying cisplatin- and pemetrexed-induced autophagy, cellular senescence, and apoptosis in A549 cells. A: Drug treatment enhances reactive oxygen species (ROS)-mediated DNA damage to trigger apoptosis and induce cellular senescence. B: Drug treatment suppresses the KRAS proto-oncogene, GTPase (KRAS)/Raf proto-oncogene, serine/threonine kinase (RAF)/ mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) signaling pathway to induce apoptosis. C: Cisplatin and pemetrexed induce autophagy in A549 cells through the regulation of the AKT serine/threonine kinase 1 (AKT)/mechanistic target of rapamycin kinase (mTOR) and AMP-activated protein kinase (AMPK)/mTOR signaling pathways.