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Hypoxia Induces Paclitaxel-Resistance through ROS Production

  • Oh, Jin-Mi (Department of Bioscience and Biotechnology, Sejong University) ;
  • Ryu, Yun-Kyoung (Department of Bioscience and Biotechnology, Sejong University) ;
  • Lim, Jong-Seok (Department of Biological Sciences, Sookmyung Women's University) ;
  • Moon, Eun-Yi (Department of Bioscience and Biotechnology, Sejong University)
  • Received : 2010.01.27
  • Accepted : 2010.02.24
  • Published : 2010.04.30

Abstract

Oxygen supply into inside solid tumor is often diminished, which is called hypoxia. Many gene transcriptions were activated by hypoxia-inducible factor (HIF)-$1{\alpha}$. Here, we investigated the effect of hypoxia on paclitaxel-resistance induction in HeLa cervical tumor cells. When HeLa cells were incubated under hypoxia condition, HIF-$1{\alpha}$ level was increased. In contrast, paclitaxel-mediated tumor cell death was reduced by the incubation under hypoxia condition. Paclitaxel-mediated tumor cell death was also inhibited by treatment with DMOG, chemical HIF-$1{\alpha}$ stabilizer, in a dose-dependent manner. A significant increase in intracellular ROS level was detected by the incubation under hypoxia condition. A basal level of cell density was increased in response to 10 nM $H_2O_2$. HIF-$1{\alpha}$ level was increased by treatment with various concentration of $H_2O_2$. The increased level of HIF-$1{\alpha}$ by hypoxia was reduced by the treatment with N-acetylcysteine (NAC), a well-known ROS scavenger. Paclitaxel-mediated tumor cell death was increased by treatment with NAC. Taken together, these findings demonstrate that hypoxia could play a role in paclitaxel-resistance induction through ROS-mediated HIF-$1{\alpha}$ stabilization. These results suggest that hypoxia-induced ROS could, in part, control tumor cell death through an increase in HIF-$1{\alpha}$ level.

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