Synergistic and antagonistic combinations of drugs in XXXX @entity263 cell lines in vitro.

@entity1 @entity632 @entity263 @entity902 @entity4349 @entity3003 @entity1259 @entity900 @entity1206 @entity2879 @entity205 @entity98 @entity1968 @entity1205 @entity5049
Microtubulin binding agents such as @entity1205 have significant preclinical and clinical activity in the treatment of @entity263 . We have previously used median-effect analysis to define both synergistic and antagonistic drug combinations which may be of value in management of @entity1 disease. These studies extend our findings in @entity263 cell lines. A semi-automated microtiter culture system was used. @entity1205 was combined with 18 other agents, incubated with DU 145, LnCaP or @entity5049 @entity263 cell lines for 72 h and the cells then incubated with @entity98 to determine cytotoxic effect. Both doublet and triplet combinations were examined. Synergy and antagonism as measured by the combination index were determined for each combination. The non-mutually exclusive criterion was applied. @entity1205 demonstrated cytotoxic additive effects or synergy with - @entity1968 , @entity205 and @entity1206 in all three cell lines. @entity1205 combined with either @entity1259 or @entity632 displayed cytotoxic synergistic effects in hormone-refractory DU 145 and @entity5049 cell lines. In contrast, drugs which have been combined clinically to treat @entity263 , i.e. @entity900 , @entity3003 or @entity2879 , were antagonistic when combined with @entity1205 . We conclude that combinations of @entity1205 with either - @entity1968 or @entity1206 may offer an enhanced cytotoxic effect in the management of @entity263 and need to be evaluated for therapeutic effect. The combination of @entity1205 with an @entity4349 was also synergistic in the two hormone-refractory cell lines, DU 145 and @entity5049 , thus suggesting a potential role in advanced disease after endocrine failure. Combinations of @entity1205 with @entity902 or @entity2879 may lead to subadditive effects in treatment.
