Lung cancer is the leading cause of cancer death. Non Small Cell Lung cancer (NSCLC) accounts for over 80% of newly diagnosed cases. NSCLC is extremely resistant to chemotherapeutic agents, such as cisplatin and paclitaxel. Those agents act mainly through activation of p53, which can largely change the response. Recent literature indicates p53 as an important regulator of the inflammatory enzyme cyclooxygenase-2 (COX-2), which has been shown to contribute actively to cancer progression. It has been proposed that specific inhibition of COX-2 may increase the citotoxic effect of chemotherapeutic agents. The main objective of this work is to analyze the effect of chemotherapy on the expression of COX-2, in different status of TP53. We have also evaluated the use of selective COX-2 inhibitors as adjuvant of chemotherapy. We used NSCLC cell lines with different TP53 mutational status: wild type (H460 and A549), mutant (ACC-LC-94) and null (ACC-LC-319 and Calu-1). Cells were treated with chemotherapeutic agents (cisplatin and paclitaxel) and/or COX-2 selective inhibitor (celecoxib). COX-2 mRNA expression was analyzed in NSCLC cell by semi-quantitative RT-PCR in parallel with quantitative analysis through TaqMan®-based real time PCR. Protein expression of COX-2, p53 and p21 (p53-target gene) was investigated by western blotting. MTT assay was used to determine drug effect on cell proliferation with determination of IC₅₀. It has been found that both cisplatin and paclitaxel are able to induce COX-2 protein expression after 30h only in cell lines that exhibit wild-type p53. Furthermore, accumulation of p53 protein was indeed verified after drug treatment (about 10h), as well as its target gene p21 (after 24h). RT-PCR has shown a 10-fold increase in mRNA COX-2 after cisplatin treatment of A549 and H460. For paclitaxel treatment, it has been observed 2- and 5-fold increase in COX-2 expression in H460 and A549, respectively. The drug concentration used for cell treatment was determined after IC₅₀ confirmation. Surprisingly, cell proliferation was not affected by the addition of celecoxib to the conventional treatment. Further analyses are being carried out to elucidate these questions. Overall, the results suggest that chemotherapy can induce COX-2 only in cells expressing active p53. Since COX-2 is considered an anti-apoptotic protein its overexpression in cancer would be extremely undesired.