The impact of COX-2 on invasion of osteosarcoma cell and its mechanism of regulation

BACKGROUND: Recently, cyclooxygenase-2 (COX-2) has become an important new target in the field of tumor metastasis. However, the relationship between COX-2 gene expression and the behavior of osteosarcoma metastasis is largely unknown. The study is to investigate how antisense oligonucleotides (ODNs) of COX-2 inhibit the invasion of human osteosarcoma cell line OS-732 and their mechanism of regulation. METHODS: A COX-2 antisense oligonucleotide was designed, synthesized, and transfected into OS-732 human osteosarcoma cells. RT-PCR and western blotting were performed to determine the transfection efficiency. A modified Boyden-transwell assay was used to measure the inhibition rate of tumor cell invasion. In OS-732 cells transfected with COX-2 antisense ODNs, RT-PCR was used to examine the mRNA expression of urokinase-type plasminogen activator (uPA) and that of its receptor, uPAR. RESULTS: Both the mRNA and protein expression levels of COX-2 were significantly reduced when cells were transfected with COX-2 antisense ODNs, which significantly reduced the invasive ability of OS-732 cells in a dose-dependent manner. The expression levels of uPA and uPAR were also significantly reduced (p < 0.01). CONCLUSION: COX-2 antisense ODNs significantly inhibited the invasion of OS-732 cells, primarily by decreasing the mRNA expression of uPA and uPAR.