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.