Antitumor effects of a cyclooxygenase-2 inhibitor, meloxicam, alone and in combination with radiation and/or 5-fluorouracil in cultured tumor cells

Abstract

To ascertain whether meloxicam used in a clinical setting as a non-steroidal anti-inflammatory drug (NSAID) warrants preclinical in vivo evaluation as an anticancer agent, we investigated its antitumor effects alone and in combination with radiation and/or 5-fluorouracil (5-FU) in cultured cells. Seven cell lines were examined for cyclooxygenase-2 (COX-2) protein expression by immunoblot analysis, and the HeLaS3, SCCVII and EMT6 cell lines were selected, expressing relatively high, intermediate, and relatively low COX-2 levels, respectively. Antitumor effects were examined using a colony assay. Among the three cell lines, the effect of meloxicam alone was strongest in SCCVII cells. With 24 h of drug exposure, meloxicam at concentrations of 250 and 1250 µM had a definite antitumor effect, dependent on the drug exposure time. The effect of meloxicam in combination with radiation and/or 5-FU was also investigated in the SCCVII cells. At a meloxicam concentration of 250 µM, the antitumor effect in combination with radiation or 5-FU was increased compared to the effect of radiation or 5-FU alone; however, the combined effect appeared to be additive. At lower concentrations, meloxicam had no radiosensitizing effect, nor did it enhance the effect of 5-FU. A meloxicam concentration of 250 µM is considerably higher than concentrations obtained in humans taking meloxicam as an NSAID. In conclusion, the antitumor effect of meloxicam was not correlated with the level of COX-2 protein expression. The effect of meloxicam in combination with radiation and/or 5-FU appeared to be additive. To evaluate the possibility of using meloxicam as an anticancer agent, in vivo investigations at clinically relevant drug dose levels are required.