Effects of a Selective Cyclooxygenase-2 Inhibitor on Cancer Cells In Vitro

Abstract

The cyclooxygenase (COX) family of enzymes has been implicated in cell proliferation and angiogenesis in many tumors, including colon cancer. Indeed, cyclooxygenase-2 (COX-2) inhibitors recently have been approved for use for prophylaxis in individuals with familial adenomatous polyposis. We now report on the effects of a selective COX-2 inhibitor, celecoxib, on cell proliferation, matrix metalloproteinase (MMP) concentration, angiogenesis using an in vitro assay, and apoptosis in several human cancer cell lines. We demonstrate that celecoxib modestly reduces proliferation in some cell lines and does not affect MMP concentrations. However, celecoxib significantly decreases microtubule formation in stimulated human umbilical vein endothelial cells (HUVECs) exposed to cancer cell supernatants, an in vitro angiogenesis model, when compared to controls incubated with supernatants from untreated cells. Celecoxib does not consistently induce apoptosis in these cell lines, as determined by DNA laddering in agarose gels and by a caspase assay. Thus, it appears that COX-2 inhibitors have beneficial effects in reducing malignant cell behavior in vitro and warrant further study to elucidate their mechanisms of action and to examine their mechanisms of action in this role and their utility in vivo in a variety of animal and human tumors.

Eicosanoid metabolism in squamous cell carcinoma cell lines derived from primary and metastatic head and neck cancer and its modulation by celecoxib

“…21 However, a controversy has been raised by reports that COX-2 inhibitors may act independently of inhibition of PG synthesis. 11,13,14,30,31 Our data show that much higher concentrations of celecoxib are needed to suppress cell growth in vitro than those achievable in humans. On the other hand, concentrations required for the inhibition of PGE 2 synthesis in vitro are clinically attainable.…”

“…27 Although the most likely antitumoral effects of NSAIDs are based on the blockade of PG synthesis, accumulating evidence suggests that mechanisms of action may not be exclusively mediated by inhibition of COX activity. 11,13,[28][29][30][31] In this study we analyzed eicosanoid metabolites and related enzymes in pairs of HNSCC cell lines derived from primary and recurrent or metastatic tumor samples of the same patient. We found a correlation between PGE 2 production and COX-2 expression, which appeared to be higher in HNSCC cell lines derived from metastasis.…”

Celecoxib inhibits meningioma tumor growth in a mouse xenograft model

“…These findings agree with those of other in vivo solid tumor studies (eg, colorectal, prostate, lung, squamous cell carcinoma, breast) showing decreased tumor size with celecoxib treatment. [30][31][32][33][34][35][36] Studies consistently show that selective COX-2 inhibitors reduce angiogenesis, probably via direct inhibition of the COX-2 enzyme.…”

Inflammatory response and meningioma tumorigenesis and the effect of cyclooxygenase-2 inhibitors

“…These findings agree with the results reported in other in vivo solid tumor studies (for example, colorectal, prostate, lung, squamous cell carcinoma, and breast) showing decreased tumor size with celecoxib treatment. 8,12,18,20,38,39,47 Analysis of tumors grown in mice and treated with highdose celecoxib showed decreased microvascular density (by 23 to 78%) and diminished Cox-2 and VEGF staining (Fig. 4), as well as increased apoptosis.…”