Therapeutic effect of the GSK3beta-inhibiting drugs against gastrointestinal cancer and the elucidation of a molecular mechanism

GSK3β抑制药物对胃肠癌的治疗作用及分子机制的阐明

• 批准号: 23591955
• 负责人: HIROSE Mayumi
• 金额: $ 3.41万
• 依托单位: Kanazawa University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2013
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23591955/
• 关键词: 消化器がん; 大腸がん; すい臓がん; GSK3beta; Drug repositioning; 医薬品; 細胞運動; 細胞増殖; GSK3β; 抗がん剤; 薬剤スクリーニング

GSK3beta is a serine/threonine protein kinase that implicated in diseases including cancer. To date, there are no clinical trial reports describing the use of specific GSK3beta inhibitors for cancer, while our results of basic research have identified GSK3beta as a tumor promoter and druggable target for cancer treatment. Several drugs prescribed for diseases other than cancer were shown to have an inhibitory effect against GSK3beta. Here we show that inhibition of GSK3beta by using these drugs, alone or in combination, compromises survival, proliferation, migration and invasion of human colon and pancreatic cancer cells. We also show that the combination of GSK3beta-inhibiting drugs is more effective than the single agent treatment against both types of cancer cell lines. Our findings warrant further investigation and preclinical study on the effective combination of GSK3beta-inhibiting drugs and that with chemotherapeutic agents for treatment of gastrointestinal cancer.

GSK3BETA是一种丝氨酸/苏氨酸蛋白激酶，与包括癌症在内的疾病有关。迄今为止，还没有临床试验报告描述了特定的GSK3BETA抑制剂用于癌症，而我们的基础研究结果已将GSK3BETA鉴定为肿瘤启动子和可药物治疗的靶标。证明除癌症以外的其他疾病中规定的药物对GSK3BETA具有抑制作用。在这里，我们表明，通过单独或组合使用这些药物来抑制GSK3BETA，从而损害了人类结肠和胰腺癌细胞的生存，增殖，迁移和侵袭。我们还表明，GSK3BETA抑制药物的组合比两种类型的癌细胞系的单一药物治疗更有效。我们的发现值得进一步研究和临床前研究，该研究对GSK3BETA抑制药物的有效组合以及与化学治疗剂治疗胃肠道癌的有效组合。

项目成果

Glycogen synthase kinase 3β inhibition sensitizes pancreatic cancer cells to gemcitabine

• DOI: 10.1007/s00535-011-0484-9
• 发表时间: 2012-03-01
• 期刊: JOURNAL OF GASTROENTEROLOGY
• 影响因子: 6.3
• 作者: Shimasaki, Takeo;Ishigaki, Yasuhito;Motoo, Yoshiharu
• 通讯作者: Motoo, Yoshiharu