Cyclooxygenase (COX) -2 is an inducible form of COX, and it involves in inflammation. In addition, Malignant mesothelioma (MM) is a fatal malignancy with an estimated incidence of 3,000 cases per year in the United States. MM occurs in the context of asbestos exposure and chronic inflammation. It would enhance the expression of inducible enzymes COX. COX-2 is an inducible enzyme responsible for prostaglandin-E2 (PGE2) production at sites of inflammation. Furthermore, cyclooxygenase activity occurs in cultured human MM cells and COX-2 is induced by inflammatory cytokines. Nevertheless, COX-2 expression is a strong prognostic factor in human MM. Moreover, it contributes independently to the other clinical and histopathological factors in determining a short survival. In this study, Rofecoxib is a potent, specific and orally active COX-2 inhibitor.
Rofecoxib is a potent COX-2 inhibitor. It potentiates the effect of Gefitinib in MM cell lines.
Rofecoxib has the IC50s of 26 and 18 nM for human COX-2 in human osteosarcoma cells and Chinese hamster ovary cells. In addition, it shows a 1000-fold selectivity for COX-2 over human COX-1 (IC50 > 50 μM in U937 cells and > 15 μM in Chinese hamster ovary cells). Meanwhile, Rofecoxib causes a cell proliferation of 68% in MPP89, 58% in Ist-Mes-1 and 40% in Ist-Mes-2. MSTO-211H and NCI-H2452 treated with 36 μM of Rofecoxib have a survival of 97% and 90% respectively. Furthermore, Rofecoxib decreases COX-2 and mRNA levels in Ist-Mes-1, Ist-Mes-2, and MPP89 cell lines. Moreover, Rofecoxib reduces the blood vessels attached to the internal limiting membrane (ILM) in mice. Rofecoxib is also an anti-inflammatory agent to treat rheumatoid arthritis.
In summary, Rofecoxib is a potent COX-2 inhibitor. It not only represents a new therapeutic class of anti-inflammatory agents for the treatment of the symptoms of osteoarthritis and rheumatoid arthritis with improved gastrointestinal tolerability. Rofecoxib potentiates the effect of Gefitinib in MM cell lines.
Stoppoloni D, et al. Mol Cancer. 2010 Feb 2;9:27.