Radiosensitizing potential of the selective cyclooygenase-2 (COX-2) inhibitor meloxicam on human glioma cells

The COX-2 protein is frequently overexpressed in human malignant gliomas. This expression has been associated with their aggressive growth characteristics and poor prognosis for patients. Targeting the COX-2 pathway might improve glioma therapy. In this study, the effects of the selective COX-2 inhibitor meloxicam alone and in combination with irradiation were investigated on human glioma cells in vitro. A panel of three glioma cell lines (D384, U87 and U251) was used in the experiments from which U87 cells expressed constitutive COX-2. The response to meloxicam and irradiation (dose-range of 0–6 Gy) was determined by the clonogenic assay, cell proliferation was evaluated by growth analysis and cell cycle distribution by FACS. 24–72 h exposure to 250–750 μM meloxicam resulted in a time and dose dependent growth inhibition with an almost complete inhibition after 24 h for all cell lines. Exposure to 750 μM meloxicam for 24 h increased the fraction of cells in the radiosensitive G2/M cell cycle phase in D384 (18–27%) and U251 (17–41%) cells. 750 μM meloxicam resulted in radiosensitization of D384 (DMF:2.19) and U87 (DMF:1.25) cells, but not U251 cells (DMF:1.08). The selective COX-2 inhibitor meloxicam exerted COX-2 independent growth inhibition and radiosensitization of human glioma cells

Combination therapy using the cyclooxygenase-2 inhibitor Parecoxib and radioimmunotherapy in nude mice with small peritoneal metastases of colonic origin.

Contains fulltext : 51280.pdf (publisher's version ) (Closed access)BACKGROUND: Inhibition of the COX-2 enzyme has been shown to have a radiosensitizing effect in epithelial cancers. The aim of this study was to investigate whether the efficacy of radioimmunotherapy (RIT) using 131I-labeled anti-CEA monoclonal antibody MN-14 could be enhanced by co-administration of the selective COX-2 inhibitor Parecoxib in mice with small volume (1-3 mm) peritoneal carcinomatosis of colonic origin. METHODS: First, the efficacy of 14 daily injections of Parecoxib monotherapy (0-0.2-1.0-5.0-25.0 mg/kg) was determined in mice with intraperitoneal LS174T xenografts. Second, the influence of Parecoxib (1.0 or 5.0 mg/kg) on the biodistribution of 125I-MN-14 was assessed. Finally, the efficacy of RIT alone [125 microCi 131I-MN-14/mouse approximately 1/4 of the maximal tolerated dose (MTD)] was compared with that of Parecoxib monotherapy and RIT combined with daily injections of Parecoxib (1.0 or 5.0 mg/kg). RESULTS: Parecoxib had no measurable antitumor effect up to the highest dose level (25 mg/kg). Parecoxib had no effect on the uptake of 125I-MN-14 in the intraperitoneal tumor xenografts or on normal tissue distribution. Median survival of the control mice and the mice treated with Parecoxib monotherapy (1.0 or 5.0 mg/kg) was 48.5 days, 52 days and 52 days (P=0.47). RIT alone significantly delayed the growth of the intraperitoneal xenografts resulting in a median survival of 87 days (P<0.0001). Mice treated with RIT + Parecoxib at 1.0 or 5.0 mg/kg had a median survival of 73.5 days and 76 days, respectively, which was not statistically different from survival after RIT alone (P=0.15). CONCLUSION: The COX-2 inhibitor Parecoxib does not enhance the therapeutic efficacy of RIT of experimental small volume peritoneal carcinomatosis of colonic origin