Hypoxia confers protection against apoptosis via PI3K/Akt and ERK pathways in lung cancer cells.
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.
Lee
Sang-Min
SM
Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul National University College of Medicine, Seoul 110-799, South Korea.
Lee
Choon-Taek
CT
Kim
Young Whan
YW
Han
Sung Koo
SK
Shim
Young-Soo
YS
Yoo
Chul-Gyu
CG
D017209:Apoptosis; D045744:Cell Line, Tumor; D002470:Cell Survival; D053938:DNA Fragmentation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005047:Etoposide / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D005434:Flow Cytometry; D006801:Humans; D000860:Hypoxia; D008175:Lung Neoplasms / Q000201:enzymology* / Q000378:metabolism / Q000473:pathology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D014466:Ultraviolet Rays
D004791:Enzyme Inhibitors; D005047:Etoposide; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases