Apoptosis of non-small-cell lung cancer cell lines after paclitaxel treatment involves the BH3-only proapoptotic protein Bim

Cell Death Differ. 2005 Mar;12(3):292-303. doi: 10.1038/sj.cdd.4401554.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Apoptosis / physiology*
  • Apoptosis Regulatory Proteins
  • Bcl-2-Like Protein 11
  • Carcinoma, Non-Small-Cell Lung
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Caspase Inhibitors
  • Caspases / metabolism
  • Cell Division / drug effects
  • Cell Line, Tumor
  • Enzyme Activation
  • Female
  • G2 Phase / drug effects
  • Humans
  • Lung Neoplasms
  • Male
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Microtubules / drug effects
  • Microtubules / physiology
  • Mitochondria / drug effects
  • Mitochondria / metabolism
  • Paclitaxel / pharmacology*
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / metabolism*
  • Proto-Oncogene Proteins c-bcl-2 / biosynthesis
  • RNA, Small Interfering / metabolism
  • Signal Transduction
  • Tumor Suppressor Protein p53 / metabolism


  • Antineoplastic Agents
  • Apoptosis Regulatory Proteins
  • BCL2L11 protein, human
  • Bcl-2-Like Protein 11
  • Carrier Proteins
  • Caspase Inhibitors
  • Membrane Proteins
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • RNA, Small Interfering
  • Tumor Suppressor Protein p53
  • Caspases
  • Paclitaxel