銅キレート剤トリエンチンの抗血管新生作用と肝癌発育および肝発癌抑制効果の検討
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概要
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Angiogenesis is now recognized to play a pivotal role in tumordevelopment, and even in the process of carcinogenesis. Trientine dihydrochloride(trientine) is used in clinical practice as a copper (Cu)-chelating agent. In this study, weelucidate that the effect of trientine on tumor development and carcinogenesis is due tothe suppression of angiogenesis in the murine hepatocellular carcinoma cell (HCC)xenograft model and in the rat hepatocarcinogenesis model, respectively. Trientinesuppressed the tumor development associated with suppression of intra-tumoralangiogenesis. Trientine treatment also resulted in a marked increase of apoptosis in thetumor, although tumor cell proliferation itself was not altered. In vitro studies alsoshowed that trientine is not cytotoxic for the tumor cells, but it significantly suppressedthe endothelial cell proliferation. In a diethylnitrosamine (DEN)-induced rathepatocarcinogenesis model, trientine treatment significantly suppressed glutathioneS-transferase placental form (GST-P)-positive preneoplastic lesions. Trientine alsomarkedly suppressed neovascularization in the liver to a similar level as that ofdevelopment of preneoplastic lesions. On the contrary, the intrahepatic cell proliferationwas not altered with or without trientine treatment. These results suggested that Cuplays a pivotal role in HCC tumor development and carcinogenesis via angiogenesissuppression. Since trientine is already used in clinical practice without any serious sideeffects, it may be an effective new strategy for future HCC therapy.
- 奈良医学会の論文
- 2004-10-31
奈良医学会 | 論文
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