Mechanism of HIF-1alpha-dependent suppression of hypoxia-induced apoptosis in squamous cell carcinoma cells.
作者： Eri Sasabe , Yukihiro Tatemoto , Dechao Li , Tetsuya Yamamoto , Tokio Osaki
DOI: 10.1111/J.1349-7006.2005.00065.X
关键词:
摘要: The transcriptional factor hypoxia-inducible factor-1 (HIF-1) plays an important role in solid tumor cell growth and survival. Overexpression of HIF-1alpha has been demonstrated many human tumors predicts a poor response to chemoradiotherapy. We examined the HIF-1alpha-induced survival pathways oral squamous carcinoma (OSCC) lines. results showed that forced expression suppressed hypoxia-induced apoptosis OSCC lines by inhibiting cytochrome c release from mitochondria. inhibited generation reactive oxygen species (ROS), elevation intracellular Ca(2+) concentration, reduction mitochondrial membrane potential, cytosolic accumulation c, which resulted inactivation caspase-9 caspase-3. In addition, antiapoptotic Bcl-2 Bcl-X(L) levels were increased pro-apoptotic Bax Bak decreased HIF-1alpha-overexpressing line. also phosphorylation Akt extracellular signal-regulated kinases (ERK). These findings indicate prevents apoptotic death through two mechanisms, including inhibition activation ERK.
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