Paclitaxel and vinorelbine cause synergistic increases in apoptosis but not in microtubular disruption in human lung adenocarcinoma cells (A-549).
Concurrent administration of paclitaxel and vinorelbine results in cytotoxicity in vivo and in vitro in a number of tumor cell lines, yet the mechanisms of enhanced cell killing are undefined. In studies here, we show that low concentrations (1 nM) of paclitaxel and vinorelbine in combination result in enhanced cell killing by apoptosis ( P<0.05) in the human lung adenocarcinoma cell line, A-549. In contrast, necrotic cell death and formation of multinucleated cells, which were significantly increased by paclitaxel ( P<0.05) alone, but not vinorelbine, were not increased synergistically by both drugs. Paclitaxel also caused microtubular disruption which was not observed with vinorelbine. These data provide further rationale for the combined use of paclitaxel and vinorelbine in clinical trials, and suggest that the cooperative effects of drugs on apoptosis are not mediated through similar disruptional effects on microtubules.
Jung
Michael
M
Department of Pathology, University of Vermont College of Medicine, 89 Beaumont Avenue, Burlington, VT 05405, USA.
Grunberg
Steven
S
Timblin
Cynthia
C
Buder-Hoffman
Sylke
S
Vacek
Pamela
P
Taatjes
Douglas J
DJ
Mossman
Brooke T
BT
D000230:Adenocarcinoma / Q000188:drug therapy / Q000473:pathology*; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D004357:Drug Synergism; D005434:Flow Cytometry; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000473:pathology*; D018613:Microscopy, Confocal; D008870:Microtubules / Q000187:drug effects* / Q000648:ultrastructure; D017239:Paclitaxel / Q000494:pharmacology*; D014747:Vinblastine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000077235:Vinorelbine
D000972:Antineoplastic Agents, Phytogenic; D004338:Drug Combinations; D014747:Vinblastine; D017239:Paclitaxel; D000077235:Vinorelbine