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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.

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