Overcoming S-phase checkpoint-mediated resistance: sequence-dependent synergy of gemcitabine and 7-ethyl-10-hydroxycamptothecin (SN-38) in human carcinoma cell lines.

ABSTRACT: Although agents that inhibit DNA synthesis are widely used in the treatment of cancer, the optimal method for combining such agents and the mechanism of their synergy is poorly understood. The present study examined the effects of combining gemcitabine (2',2'-difluoro 2'-deoxycytidine) and 7-ethyl-10-hydroxycamptothecin (SN-38; the active metabolite of irinotecan), two S-phaseselective agents that individually have broad antitumor activity, in human cancer cells in vitro. Colony-forming assays revealed that simultaneous treatment of Ovcar-5 ovarian cancer cells or BxPC-3 pancreatic cancer cells with gemcitabine and SN-38 resulted in antagonistic effects. In contrast, sequential treatment with these two agents in either order resulted in synergistic anti-proliferative effects, although the

SUBMITTER: Galvez-Peralta M 

PROVIDER: S-EPMC2574763 | biostudies-literature | 2008 Sep

REPOSITORIES: biostudies-literature