Inhibition of Transforming Growth Factor-β, Hypoxia-inducible Factor-1α and Vascular Endothelial Growth Factor Reduced Late Rectal Injury Induced by Irradiation
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概要
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Tumor hypoxia and angiogenesis associated with malignant progression have been studied widely. The efficacy of angiogenesis inhibition combined with radiotherapy has been demonstrated in cancer treatment. Here, we studied the effect of hypoxia and angiogenesis inhibition on radiation-induced late rectal injury. The rectum of C57BL/6N mice was irradiated locally with a single dose of 25 Gy. Radiation-induced histological changes were examined at 90 days after irradiation by hematoxylin-eosin (H.E.) staining and azan staining. Pimonidazole was administered and its distribution was assayed by immunohistochemistry staining. Expression of transforming growth factor β1 (TGF-β1), hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF) was assessed on the fibrotic region using real-time PCR and immunohistochemistry. In addition, the effects of TGF-β, VEGF and HIF-1α on radiation-induced injury were investigated by the administration of neutralizing antibody of TGF-β, antibody of VEGF or YC-1 (3-(5-hydroxymethyl-2-furyl)-1-benzylindazole) which was developed as an agent for inhibiting HIF-1 expression after irradiation respectively. Fibrosis and uptake of pimonidazole were found 90 days after irradiation. The expression of TGF-β1, HIF-1α and VEGF significantly increased with the formation of fibrosis induced by irradiation compared with unirradiated controls. In addition, treatment of neutralizing antibody of TGF-β, antibody of VEGF or YC-1 reduced the development of radiation-induced injury. Our results suggested that radiation-induced hypoxia may play an important role in late rectal injury. Although the inhibition of HIF-1α and VEGF reduced the radiation induced late injury, the precise mechanism is still unclear.
- 日本放射線影響学会の論文
- 2009-05-16
著者
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Kijima Hiroshi
Department of Pathology, Hirosaki University School of Medicine
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ONO Koji
Particle Radiation Oncology Research Center, Research Reactor Institute, Kyoto University
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Nakane Akio
Department of Microbiology and Immunology, Hirosaki University Graduate School of Medicine
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Liu Yong
Particle Radiation Oncology Research Center Kyoto University
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Liu Yong
Particle Radiation Oncology Research Center Research Reactor Institute Kyoto University
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KUDO Kohsei
Department of Radiological Life Sciences, Hirosaki University Graduate School of Health Sciences
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HU Dong-Liang
Department of Microbiology and Immunology, Hirosaki University Graduate School of Medicine
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LIU Yong
Departments of Radiology and Radiation Oncology, Hirosaki University Graduate School of Medicine
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ABE Yoshinao
Departments of Radiology and Radiation Oncology, Hirosaki University Graduate School of Medicine
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Ono Koji
Particle Radiation Oncology Research Center Kyoto University
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Nakane Akio
Department Of Microbiology And Immunology Hirosaki University Graduate School Of Medicine
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Kijima Hiroshi
Department Of Pathology And Bioscience Hirosaki University Graduate School Of Medicine
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Kudo Kohsei
Department Of Radiological Life Sciences Hirosaki University Graduate School Of Health Sciences
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Kudo Kohsei
Department Of Radiological Life Sciences Division Of Medical Life Sciences Hirosaki University
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Liu Yong
Department Of Applied Chemistry School Of Engineering University Of Toyama
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Nakane Akio
Department Of Bacteriology Hirosaki University School Of Medicine
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Ono Koji
京都大学原子炉実験所附属粒子線腫瘍学研究センター
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Hu Dong-liang
Department Of Microbiology And Immunology Hirosaki University Graduate School Of Medicine
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Abe Yoshinao
Department Of Radiology And Radiation Oncology Hirosaki University
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Abe Yoshinao
Department Of Nuclear Medicine And Radiology Division Of Brain Sciences Institute Of Development Agi
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Kijima Hiroshi
Department Of Hematology/oncology Tokai University School Of Medicine
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Liu Yong
Department Of Anatomy School Of Medicine Xi'an Jiaotong University
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