AT-406, an IAP Inhibitor, Activates Apoptosis and Induces Radiosensitization of Normoxic and Hypoxic Cervical Cancer Cells
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概要
- 論文の詳細を見る
IAP antagonists increased the antitumor efficacy of X-irradiation in some types of cancers, but their effects on hypoxic cancer cells remain unclarified. We aims to investigate the radiosensitizing effect of an IAP inhibitor AT-406 on cervical cancer cell lines under both normoxia and hypoxia conditions. Hela and Siha cells were treated to investigate the effects of drug administration on cell proliferation, apoptosis, and radiosensitivity. Western blot analysis was used to determine the role of AT-406 in inhibition of IAPs. The pathway of apoptosis was characterized by caspases activity assay. AT-406 potently sensitized Hela cells but not Siha cells to radiation under normoxia. Notably, the radiosensitizing effect of AT-406 on hypoxic cells was more evident than on normoxic cells in both cell lines. Further mechanism studies by western blot showed that under normoxia AT-406 decreased the level of cIAP1 in Hela cells in a dose-dependent manner; while additional downregulation of XIAP expression was induced by AT-406 treatment under hypoxia in both cell lines. Finally, AT-406 works on both extrinsic death receptor and intrinsic mitochondrial apoptosis pathways to activate apoptosis. Totally, AT-406 acts as a strong radiosensitizer in human cervical cancer cells, especially in hypoxic condition.
- 公益社団法人 日本薬理学会の論文
著者
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Yang Xi
Department Of Genetics And Developmental Biology The Fourth Military Medical University
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Liu Jia
Department Of Chemistry And Biochemistry University Of Maryland
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Cai Jing
Department Of Anatomy And Cell Biology The University Of Western Ontario
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Wang Di
Department Of Dermatovenereology Peking University First Hospital
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LU Jing
Department of Electrical and Computer Engineering, University of California
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Sun Xin-Chen
Department of Radiation Oncology, the First Affiliated Hospital of Nanjing Medical University, China
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Liu Jia
Department of Radiation Oncology, the First Affiliated Hospital of Nanjing Medical University, China
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Qin Qin
Department of Radiation Oncology, the First Affiliated Hospital of Nanjing Medical University, China
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Zhan Liang-Liang
Department of Radiation Oncology, the First Affiliated Hospital of Nanjing Medical University, China
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Zhu Hong-Cheng
Department of Radiation Oncology, the First Affiliated Hospital of Nanjing Medical University, China
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Zhang Chi
Department of Radiation Oncology, the First Affiliated Hospital of Nanjing Medical University, China
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Xu Li-Ping
Department of Radiation Oncology, the First Affiliated Hospital of Nanjing Medical University, China
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Liu Zhe-Ming
Department of Radiation Oncology, the First Affiliated Hospital of Nanjing Medical University, China
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Cui He-Qing
Department of Radiation Oncology, the Second People's Hospital of Lian Yungang, Lian Yungang Hospital Affiliated to Bengbu Medical College, China
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Meng Ciu-Ciu
Department of Radiation Oncology, the Second People's Hospital of Lian Yungang, Lian Yungang Hospital Affiliated to Bengbu Medical College, China
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Cheng Hong-Yan
Department of Synthetic Internal Medicine, the First Affiliated Hospital of Nanjing Medical University, China
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