Inhibitive effect of celecoxib on the adhesion and invasion of human tongue squamous carcinoma cells to extracellular matrix via down regulation of MMP-2 expression

The effect of cyclooxygenase 2 (COX-2) and its inhibitor on metastasis and invasion of tumor and its relationship with matrix metalloproteinase are getting more and more attention. Down regulation of matrix metalloproteinase (MMP) expression could inhibit the invasion and adhesion ability of cancer cells. Our study observed the inhibitive effect of selective COX-2 inhibitor, celecoxib, on adhesion and invasion ability of human tongue squamous carcinoma cell line Tca8113 and its relationship with MMP-2 secretion. COX-2 expression of Tca8113 cell was detected by Western blot analysis. Ratio of COX-2 positive Tca8113 cell was determined by flow cytometry analysis. MMP-2 and PGE2 secretion was measured by ELISA. Invasion of a Matrigel-coated membrane by Tca8113 cells was quantitatively assessed by counting migrated cells. Results showed that COX-2 expression was positive in Tca8113 cell and could be significantly inhibited by celecoxib. Celecoxib could inhibit PGE2 production of Tca8113 cell in a dose-dependent manner, down-regulate MMP-2 secretion of Tca8113 cell, and at the same time significantly inhibit invasion and adhesion ability of these cells. Adding extrinsic PGE2 could antagonize the inhibitive effect of celecoxib not only on MMP-2 secretion of Tca8113 cell, but also on invasion and adhesion ability of the cells. The results suggested that celecoxib had chemoprevention effect on invasion and metastasis of oral carcinoma.

Research highlights▶ COX-2 inhibitor, celecoxib, could significantly inhibit the COX-2 protein expression of Tca8113 cells, as well as the production of downstream PGE2. ▶ This indicated that celecoxib could also inhibit the COX-2 activity meanwhile and further inhibit the PGE2 production and MMP-2 release. ▶ Adding of exogenous PGE2 could obviously antagonize such inhibitory effect of celecoxib.