The present study was undertaken to determine: 1) whether pemetrexed activates Akt in human NSCLC A549 cells; 2) the role of Akt activation in pemetrexed-mediated growth arrest and cell death; and 3) whether activation of Akt plays a role in pemetrexed-induced growth arrest and apoptotic cell death, and, if so, by what mechanisms. Here, AKT1 is linked to non-small cell lung carcinoma.