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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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Title: X Irradiation Combined with TNF α-related Apoptosis-inducing Ligand (TRAIL) Reduces Hypoxic Regions of Human Gastric Adenocarcinoma Xenografts in SCID Mice
Authors: TAKAHASHI, Momoko Browse this author
YASUI, Hironobu Browse this author
OGURA, Aki Browse this author
ASANUMA, Taketoshi Browse this author
KUBOTA, Nobuo Browse this author
TSUJITANI, Michihiko Browse this author
KUWABARA, Mikinori Browse this author
INANAMI, Osamu Browse this author →KAKEN DB
Keywords: Radiation
Solid tumor
TRAIL
Hypoxia
Xenograft
Issue Date: 26-Mar-2008
Publisher: Japan Radiation Research Society
Journal Title: Journal of Radiation Research
Volume: 49
Issue: 2
Start Page: 153
End Page: 161
Publisher DOI: 10.1269/jrr.07082
Abstract: 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.
Type: article
URI: http://hdl.handle.net/2115/33951
Appears in Collections:獣医学院・獣医学研究院 (Graduate School of Veterinary Medicine / Faculty of Veterinary Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 稲波 修

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