Inhibition of GSK-3β activity attenuates proliferation of human colon cancer cells in rodents

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概要

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• 最終稿を登録可能The authors' recent discovery that glycogen synthase kinase-3β (GSK-3β) participates in colon cancer cells' survival and proliferation prompted us to investigate whether GSK-3β inhibition alters proliferation of colon cancer cells in vivo. Groups of four or five athymic mice (Balb/c, nu/nu) with subcutaneous xenografts of SW480 human colon cancer cells were treated with dimethyl sulfoxide (DMSO) or different doses (1, 2 and 5mg/kg body weight) of either small-molecule GSK-3β inhibitor (SB-216763 and AR-A014418) by intraperitoneal injection three times per week for 5 weeks. Compared with DMSO (a diluent of the GSK-3β inhibitors) as a control, either GSK-3β inhibitor significantly inhibited proliferation of cancer cell xenografts in the rodents in a dose-dependent manner. Histochemical and immunohistochemical analysis of tumor xenografts demonstrated a significant, dose-dependent decrease in fractions of proliferating cells and an increase in the incidence of apoptosis of cancer cells in mice treated with either GSK-3β inhibitor. No adverse events or effects were observed in the rodents during the course of treatment, except for rare lethal accidents due to intraperitoneal injection. Morphological examination showed no apparent pathologic changes in major organs including the lungs, liver, pancreas, kidneys, spleen and large bowel of rodents treated with DMSO and the GSK-3β inhibitors. The results indicate that the GSK-3β inhibitors would be a novel class of therapeutic agent for colon cancer. © 2007 Japanese Cancer Association.

• Blackwell Publishing / 日本癌学会の論文
• 2007-09-10

著者

• Takahashi Yutaka

  Division Of Diabetes Metabolism And Endocrinology Department Of Internal Medicine Kobe University Gr

• Kawakami Kazuyuki

  Division Of Translational And Clinical Oncology Cancer Research Institute Kanazawa University

• Kawakami Kazuyuki

  Division Of Translational And Clinical Oncology Graduate School Of Medical Science Kanazawa Universi

• Minamoto Toshinari

  Division Of Translational And Clinical Oncology Graduate School Of Medical Science Kanazawa Universi

• Minamoto Toshinari

  Division Of Molecular Diagnostic Pathology Cancer Research Institute Kanazawa University

• Takahashi Yutaka

  Division Of Surgical Oncology Cancer Research Institute Kanazawa University

• Miyashita Katsuyoshi

  Division Of Translational And Clinical Oncology Graduate School Of Medical Science Kanazawa Universi

• OOI Akishi

  Departments of Pathology, Yamanashi Medical University

• Ooi Akishi

  Department Of Molecular And Cellular Pathology Graduate School Of Medical Science Kanazawa Universit

• YASUMOTO Kazuo

  Division of Surgical Oncology, Cancer Research Institute, Kanazawa University

• Yasumoto Kazuo

  Division Of Surgical Oncology Cancer Research Institute Kanazawa University

• Shakoori Abbas

  Division Of Translational And Clinical Oncology Graduate School Of Medical Science Kanazawa Universi

• MAI Wei

  Division of Translational and Clinical Oncology, Graduate School of Medical Science, Kanazawa Univer

• Mai Wei

  Division Of Translational And Clinical Oncology Graduate School Of Medical Science Kanazawa Universi

• Yamamoto Kazuo

  Division Of Cytokine Signaling Department Of Molecular Microbiology And Immunology Nagasaki Universi

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