Enhancement of Tumor Radioresponse by Wortmannin in C3H/HeJ Hepatocarcinoma
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概要
- 論文の詳細を見る
The objective of this study was to explore whether a specific inhibitor of PI3K, wortmannin, could potentiate the antitumor effect of radiation in vivo, particularly on radioresistant murine tumors. C3H/HeJ mice bearing syngeneic hepatocarcinoma (HCa-I) were treated with 25 Gy radiation, wortmannin, or both. Wortmannin was administered intraperitoneally (1 mg/kg) once daily for 14 days. Tumor response to treatment was determined by a tumor growth delay assay. Possible mechanisms of action were explored by examining the level of apoptosis and regulating molecules. The expression of regulating molecules was analyzed by Western blot for p53 and p21^<WAF1/CIP1>, and immunohistochemical staining for p21^<WAF1/CIP1>, CD31 and VEGF. In the tumor growth delay assay, wortmannin increased the effect of tumor radioresponse with an enhancement factor (EF) of 2.00. The level of apoptosis achieved by the combined treatments was shown to be no more than an additive effect; peak apoptotic index was 11% in radiation alone, 13% in wortmannin alone, and 19% in the combination group. Markedly increased areas of necrosis at 24 h in the combination group were noted. Western blotting showed upregulation of p21^<WAF1/CIP1> in the combination treatment group, which correlated with low levels of VEGF. Microvascular density was evidently also reduced, based on low expression of CD31. In murine hepatocarcinoma, the antitumor effect of radiation was potentiated by wortmannin. The mechanism seems to involve not only the increase of induced apoptosis but also enhanced vascular injury. Wortmannin, in combination with radiation therapy, may have potential benefits in cancer treatment.
- 日本放射線影響学会の論文
- 2007-05-15
著者
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Seong Jinsil
Departments of Radiation Oncology, Yonsei University Health System
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Kim Wonwoo
Departments of Radiation Oncology, Yonsei University Health System
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Oh Haejin
Department Of Radiation Oncology Brain Korea 21 Project For Medical Science Yonsei University Health
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Koom Woong
Department Of Radiation Oncology Brain Korea 21 Project For Medical Science Yonsei University Health
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Kim Wonwoo
Department Of Radiation Oncology Brain Korea 21 Project For Medical Science Yonsei University Health
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Kim Wonwoo
Department Of Radiation Oncology Brain Korea 21 Project For Medicine Yonsei University
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Seong Jinsil
Department Of Radiation Oncology Brain Korea 21 Project For Medical Science Yonsei University Health
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Seong Jinsil
Department Of Radiation Oncology Brain Korea 21 Project For Medicine Yonsei University
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Seong Jinsil
Department Of Radiation Oncology : Brain Korea 21 Project For Medical Science : Institute For Gastro
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OH Hae
Departments of Radiation Oncology, Yonsei University Health System
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An Jeung
Department Of Radiation Oncology Brain Korea 21 Project For Medicine Yonsei University
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AN Jung
Department of Radiation Oncology, Brain Korea 21 Project for Medicine, Yonsei University
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Oh Hae
Department Of Radiation Oncology Brain Korea 21 Project For Medicine Yonsei University
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Oh Hae
Department Of Radiation Oncology Brain Korea 21 Project For Medical Science Yonsei University Colleg
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Kim Wonwoo
Department Of Radiation Oncology Brain Korea 21 Project For Medical Science Yonsei University Colleg
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