Sequence dependence of paclitaxel (Taxol) combined with cisplatin or alkylators in human cancer cells.

摘要: Clinical trials combining paclitaxel with other active chemotherapy agents are currently underway. In vitro preclinical studies may assist in the selection of appropriate drug combinations or sequences for clinical investigation. We have used clonogenic cell survival assays and DNA flow cytometry to examine effect combined melphalan, thiotepa, cisplatin on cell-cycle parameters human lung A549 breast MCF-7 adenocarcinoma cells. cells were incubated 24 h, followed by a 1 h exposure cisplatin, thiotepa. Both types also an alkylator exposure. When preceded either cytotoxicity was additive both lines tested. given prior paclitaxel, However, alkylators antagonistic when they (e.g., 2% 100 nM vs. 7% paclitaxel). Cell-cycle analysis revealed that blocked majority into G2/M phase (> = 80% cells, 60-65% cells). before incubation reduced proportion but not G2/M--e.g., 30 micrograms/ml caused only 25% 55% block G2/M.(ABSTRACT TRUNCATED AT 250 WORDS)