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KMID : 0606920100180020145
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Biomolecules & Therapeutics
2010 Volume.18 No. 2 p.145 ~ p.151
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Hypoxia Induces Paclitaxel-Resistance through ROS Production
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Oh Jin-Mi
Ryu Yun-Kyoung
Lim Jong-Seok
Moon Eun-Yi
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Abstract
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Oxygen supply into inside solid tumor is often diminished, which is called hypoxia. Many gene transcriptions were activated by hypoxia-inducible factor (HIF)-1α. 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-1α 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-1α 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 H2O2. HIF-1α level was increased by treatment with various concentration of H2O2. The increased level of HIF-1α 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-1α stabilization. These results suggest that hypoxia-induced ROS could, in part, control tumor cell death through an increase in HIF-1α level.
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KEYWORD
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HeLa cell, Hypoxia, HIF-1α, ROS, Paclitaxel
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