Hypoxia confers protection against apoptosis via PI3K/Akt and ERK pathways in lung cancer cells

Cancer Lett. 2006 Oct 28;242(2):231-8. doi: 10.1016/j.canlet.2005.11.001. Epub 2006 Jan 19.


Hypoxia confers protection against apoptosis in cancer cells, and this hypoxia-induced resistance to apoptosis has been suggested to be associated with genetic and adaptive changes. However, it is not clear whether survival signals, such as the PI3K/Akt and ERK pathways are involved. We investigated the roles of these pathways in hypoxia-induced protection against apoptosis in lung cancer cells. Treatment of cells with either ultraviolet (UV) or etoposide induced apoptosis time-dependently in A549 and NCI-H157 cells. However, though hypoxia alone neither induced apoptosis nor reduced cell survival, it suppressed the apoptosis induced by UV or etoposide. Moreover, hypoxia activated the PI3K/Akt and ERK pathways, and blocking the activation of either pathway reversed resistance to UV- and etoposide-induced apoptosis in response to hypoxia. These results suggest that hypoxia confers resistance to UV- or etoposide-mediated apoptosis in lung cancer cells via the activations of the PI3K/Akt and the ERK pathways.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis*
  • Cell Line, Tumor
  • Cell Survival
  • DNA Fragmentation
  • Enzyme Inhibitors / pharmacology
  • Etoposide / pharmacology
  • Extracellular Signal-Regulated MAP Kinases / metabolism*
  • Flow Cytometry
  • Humans
  • Hypoxia*
  • Lung Neoplasms / enzymology*
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Ultraviolet Rays


  • Enzyme Inhibitors
  • Etoposide
  • Phosphatidylinositol 3-Kinases
  • Proto-Oncogene Proteins c-akt
  • Extracellular Signal-Regulated MAP Kinases