X Irradiation Combined with TNF α-related Apoptosis-inducing Ligand (TRAIL) Reduces Hypoxic Regions of Human Gastric Adenocarcinoma Xenografts in SCID Mice

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概要

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• Our previous study showed that X irradiation induced the expression of death receptor DR5 on the cell surface in tumor cell lines under not only normoxia but also hypoxia. X irradiation combined with TNF α-related apoptosis-inducing ligand (TRAIL), which is the ligand of DR5, induced apoptosis in vitro (Takahashi et al., (2007) Journal of Radiation Research, 48: 461-468). In this report, we examined the in vivo antitumor efficacy of X irradiation combined with TRAIL treatment in tumor xenograft models derived from human gastric adenocarcinoma MKN45 and MKN28 cells in SCID mice. X irradiation combined with TRAIL synergistically suppressed the tumor growth rates in the xenograft models derived from MKN45 and MKN28 cells, which have wild type Tp53 and mutated Tp53, respectively, indicating that the antitumor effects occurred in a Tp53-independent manner. Histological analysis showed that the combination of X irradiation and TRAIL induced caspase-3-dependent apoptotic cell death. Moreover, the immunohistochemical detection of hypoxic regions using the hypoxic marker pimonidazole revealed that caspase-3-dependent apoptosis occurred in the hypoxic regions in the tumors. These results indicated that X irradiation combined with TRAIL may be a useful treatment to reduce tumor growth in not only normoxic but also hypoxic regions.

• 2008-03-16

著者

• 浅沼 武敏

  北海道大学大学院獣医学研究科環境獣医科学講座放射線学教室

• Kubota Nobuo

  Pola Chemical Industries Inc.

• TSUJITANI MICHIHIKO

  Pola Chemical Industries, Inc.

• Kubota Nobuo

  Department Of Radiological Sciences. Ibaraki Prefectural University Of Health Sciences

• INANAMI Osamu

  Laboratory of Radiation Biology, Department of Environmental Veterinary Sciences, Graduate School of

• Kuwabara Mikinori

  弘前大学 保健学研究科放射線生命科学

• Kuwabara Mikinori

  Laboratory Of Radiation Biology Graduate School Of Veterinary Medicine

• Asanuma Taketoshi

  Laboratory Of Radiation Biology Department Of Environmental Veterinary Sciences Graduate School Of V

• Asanuma Taketoshi

  Laboratory Of Radiation Biology Department Of Environmental Veterinary Medicine Graduate School Of V

• Asanuma Taketoshi

  Depertment Of Radiation Biology Faculty Of Veterinary Medicine Hokkaido University

• Inanami Osamu

  弘前大学 保健学研究科放射線生命科学

• Inanami Osamu

  Laboratory Of Radiation Biology Department Of Environmental Veterinary Medical Sciences Graduate Sch

• Inanami Osamu

  Laboratory Of Radiation Biology Graduate School Of Veterinary Medicine Hokkaido University

• TAKAHASHI Momoko

  Laboratory of Radiation Biology, Department of Environmental Veterinary Sciences, Graduate School of

• YASUI Hironobu

  Laboratory of Radiation Biology, Department of Environmental Veterinary Sciences, Graduate School of

• OGURA Aki

  Laboratory of Radiation Biology, Department of Environmental Veterinary Sciences, Graduate School of

• KUWABARA Mikinori

  Yokohama College of Pharmacy

• KUWABARA Mikinori

  Labs. Radiat. Biol.

• Kuwabara M

  Hokkaido Univ. Sapporo Jpn

• Ogura Aki

  Laboratory Of Radiation Biology Department Of Environment Veterinary Sciences School Of Veterinary M

• Yasui Hironobu

  Laboratory Of Radiation Biology Department Of Environmental Veterinary Sciences Graduate School Of V

• Inanami Osamu

  Lab. Radiat. Biol. Grad. Sch. Vet. Med. Hokkaido Univ.

• Kuwabara Mikinori

  Lab. Radiat. Biol. Grad. Sch. Vet. Med. Hokkaido Univ.

• Takahashi Momoko

  Laboratory Of Radiation Biology Department Of Environmental Veterinary Sciences Graduate School Of V

• Tsujitani Michihiko

  Pola Chemical Industries

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