Abstract
A significant variation in susceptibility to paclitaxel-mediated killing was observed among a panel of short-term cultured non-small-cell lung cancer (NSCLC) cell lines. Susceptibility to killing by paclitaxel correlated with expression of the BH3-only protein, Bim, but not with other members of Bcl-2 family. NSCLC cell lines with the highest level of Bim expression are most susceptible to apoptosis induction after paclitaxel treatment. Forced expression of Bim increased paclitaxel-mediated killing of cells expressing an undetectable level of Bim. Conversely, knock down of Bim, but not Bcl-2 expression, decreased the susceptibility of tumor cells to paclitaxel-mediated killing. Similar observations were made using a panel of breast and prostate cancer cell lines. Paclitaxel impairs microtubule function, causes G2/M cell cycle blockade, mitochondria damage, and p53-independent apoptosis. These results established Bim as a critical molecular link between the microtubule poison, paclitaxel, and apoptosis.
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Abbreviations
- BH:
-
Bcl-2 homologous (domain)
- siRNA:
-
small interfering RNA
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Acknowledgements
We thank Dr. Stanley J Korsmeyer for providing the retroviral vectors, Dr. Walter J Urba for the critical reading of this manuscript, Dr. Bernard A Fox for his support, and Mr. Dan Haley for the cell sorting. This study was supported by grants from the Chiles Foundation, the Providence Portland Medical Foundation, the MJ Murdock Charitable Trust, and Cell Genesis Corporation.
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Li, R., Moudgil, T., Ross, H. et al. Apoptosis of non-small-cell lung cancer cell lines after paclitaxel treatment involves the BH3-only proapoptotic protein Bim. Cell Death Differ 12, 292–303 (2005). https://doi.org/10.1038/sj.cdd.4401554
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DOI: https://doi.org/10.1038/sj.cdd.4401554
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