Effect of cyclooxygenase-2 antisense oligodeoxyribonucleotides in A-549 lung cancer cells.

BACKGROUND Cyclooxygenase (COX)-2 is overexpressed in several tumor entities and seems to play a key role in carcinogenesis. This makes it a potential target in cancer therapy. MATERIALS AND METHODS Twelve phosphorothioate-modified antisense oligonucleotides (asODNs) against six targets of COX-2 mRNA were transfected to A-549 lung carcinoma cells. COX-2 mRNA and protein levels were determined by quantitative RT-PCR and flow cytometry, respectively. Cell growth was assessed by measuring Alamar Blue reduction. RESULTS The tested asODNs exhibited a range of activities. The most potent asODN reduced uninduced COX-2 mRNA to 66% and protein level to 75%, respectively. While this asODN did not influence cell growth, a 15% growth reduction was observed after transfection of another asODN which suppressed COX-2 mRNA to 71% and protein level to 84%. CONCLUSION The use of asODNs directed against COX-2 mRNA is a promising approach to inhibit COX-2 expression in tumor cells.