銅キレート剤トリエンチンはin vivoとin vitroでマウス線維肉腫にアポトーシスを誘発する

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  • HAYASHI Masanobu
    Department of Veterinary Radiology, School of Veterinary Medicine, Rakuno Gakuen University
  • NISHIYA Hide
    Department of Veterinary Radiology, School of Veterinary Medicine, Rakuno Gakuen University
  • CHIBA Toshiaki
    Department of Veterinary Radiology, School of Veterinary Medicine, Rakuno Gakuen University
  • ENDOH Daiji
    Department of Veterinary Radiology, School of Veterinary Medicine, Rakuno Gakuen University
  • KON Yasuhiro
    Laboratory of Anatomy, Graduate School of Veterinary Medicine, Hokkaido University
  • OKUI Toyo
    Hokkaido Institute of Public Health

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タイトル別名
  • Trientine, a Copper-Chelating Agent, Induced Apoptosis in Murine Fibrosarcoma Cells In Vivo and In Vitro

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Anti-copper treatments have been investigated to determine whether they suppress angiogenesis and tumor development since Cu is widely accepted as being required for angiogenesis. We examined the effects of treatment with trientine, a copper-chelating agent, on tumor development in a murine xenograft model using fibrosarcoma-derived transplantable QRsp-11 cells and C57BL/6 mice and induction of apoptosis in tumor cells and endothelial cells in vivo and in vitro. The tumor volumes increased more slowly in trientine-treated mice than in untreated mice. Tumor volumes in the treated mice were significantly smaller than those in the untreated mice at 24 days postinoculation (d.p.i.) of tumor cells. A cluster of pyknotic tumor cells and morphological abnormalities in capillary endothelial cells were observed in the tumors of trientine-treated mice but not in the tumors of untreated mice. The proportions of apoptotic and necrotic cells in the tumors of treated mice were approximately 3.5-fold higher than those in the tumors of untreated mice at 14 d.p.i. When the cells were treated with trientine in vitro, mouse endothelial cells and bovine primary endothelial cells showed an approximately 10-fold higher sensitivity to trientine than QRsp-11 cells in terms of D37. However, the proportion of apoptotic cells in endothelial cells was significantly lower than that in QRsp-11 cells after treatment with trientine. These results show that apoptosis was induced in tumor cells by treatment with trientine in vivo and in vitro.<br>

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