Abstract
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.
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Acknowledgements
This work was supported in part by a grant from Glaxo Smith Kline, Research Triangle Park, North Carolina, and a grant from the Vermont Cancer Center (VCC). The Microscopy Imaging Center is a core facility of the VCC. The authors wish to thank Ms Laurie Sabens for the typing of this manuscript and Andrew Cummins for preparation of graphics.
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Jung, M., Grunberg, S., Timblin, C. et al. Paclitaxel and vinorelbine cause synergistic increases in apoptosis but not in microtubular disruption in human lung adenocarcinoma cells (A-549). Histochem Cell Biol 121, 115–121 (2004). https://doi.org/10.1007/s00418-004-0618-8
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DOI: https://doi.org/10.1007/s00418-004-0618-8