Selective COX-2 Inhibitor (Rofecoxib) Inhibits Vinorelbine Cytotoxicity in C6 Glioma Cells In Vitro

Abstract

We examined the effects of gemcitabine, a novel nucleotide analogue, and vinorelbine, a semi-synthetic vinca alcaloid, in C6 glioma cell culture. We simultaneously monitored the modulation of its activity in combination with the te- lomerase inhibitory agent dimetilsulfoxid and with a specific cyclooxygenase-2 inhibitory agent Rofecoxib. The effects of the gemcitabine/ vinorelbine combination were observed over a 96 hour period. Plating, S-phase (bromodeoxyuridine- labelling index) and ultrastructure were selected as the evaluation parameters of drug interactions. Gemcitabine (10� g/ml) was found to possess significant blocking activity of C6 glioma plating and cells' S-phase. Vi- norelbine (10� g/ml) also demonstrated significant inhibitory activity. Vinorelbine reduced BrdU-LI but was not as effec- tive as gemcitabine. Rofecoxib (10� g/ml) showed no synergism on cell inhibition either with gemcitabine or vinorelbine and protected against the S-phase depleting activity of vinorelbine. Dimetilsulfoxid (20� g/ml) reduced the effect of vinorelbine in spheroid culture. But at the final 96 th hour tie point dimetil- sulfoxid reduced the increasing cell numbers which were previously seen in the gemcitabine group. In conclusion, both gemcitabine and vinorelbine effectively reduced both the monolayer and spheroid growth of C6 glioma cells. At the single cell level, only dimetilsulfoxid could sensitise for gemcitabine but not vinorelbine. Despite re- ducing spheroid growth, treatment using cyclooxygenase-2 inhibitors with microtubule inhibitors should be avoided.