Cyclooxygenase-2 expression is induced by celecoxib treatment in lung cancer cells and is transferred to neighbor cells via exosomes

Abstract

Lung cancer is one of most common types of cancer worldwide. Lung cancer results in a death higher rate each year compared to colon, breast and prostate cancer combined. Celecoxib is a selective inhibitor of cyclooxygenase-2 (COX-2), an enzyme of which the expression is induced by various stimuli, such as inflammation. In addition, celecoxib triggers COX-2 loading on exosomes. Exosomes are small vesicles composed of a lipid bilayer membrane and are found in most biological fluids, such as blood breast milk and urine. In this study, we focused on exosomes containing COX-2 proteins from lung cancer cells to determine their involvement in the interaction with neighbor cells following treatment with celecoxib. We found that celecoxib induced COX-2 expression in both the cytosol and exosomes in lung cancer cells. Exosomes from celecoxib-treated lung cancer cell culture supernatant were isolated and incubated with several types of cells. The THP-1, monocytic leukemia cell line effectively absorbed COX-2 by lung cancer cell-derived exosomes. Following incubation with exosomes, the COX-2 protein level was increased in the THP-1 cells; however, COX-2 mRNA expression was not affected. Moreover, prostaglandin E2 (PGE2) and vascular endothelial growth factor (VEGF) production by THP-1 cells was increased following incubation with exosomes from celecoxib-treated lung cancer cells. Conditioned medium from THP-1 following incubation with exosomes promoted formation in EA.hy926 cells. Taken together, our findings suggest that celecoxib induces COX-2 expression in lung cancer cells, and that highly expressed COX-2 in exosomes can be transferred to other cells.