Human Breast Cancer Cell DNA Synthesome Can Serve as a Novel in Vitro Model System for Studying the Mechanism of Action of Anticancer Drugs

摘要

Gemcitabine (dFdC) and cytarabine (arcC) are both analogs of deoxycytidine. In this report, we compared the effects of dFdC and' araC on in vitro DNA synthesis mediated by the DNA synthesis with the effects of these drugs on intact MCF7 cell DNA synthesis. Our results showed that dFdC was more potent than araC at inhibiting intact MCF7 cell DNA synthesis and clonogenicity. In vitro SV4O replication assays using the DNA synthesis derived from MCF7 cells demonstrated that the formation of full-length DNA along with replication intermediates were inhibited by dFdCTP and araCTP in a concentration-dependent manner. In the presence of lOmicronM dCTP, 8micronM dFdCTP were required to inhibit in vitro SV4O DNA synthesis by 50% and was I 0 fold less than araCTP. Our results also demonstrated that the DNA synthesis can serve as a model for studying the mechanism of action of anticancer drugs.