text: These data demonstrated that 1) gemcitabine and pemetrexed synergistically interact against NSCLC cells through the suppression of Akt phosphorylation and induction of apoptosis; 2) the gene expression profile of critical genes may predict for drug chemosensitivity; and 3) << pemetrexed >> enhances dCK and [[ hENT1 ]] expression, thus suggesting the role of gene-expression modulation for rational development of chemotherapy combinations.