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Development of therapeutic strategy for colorectal cancer by utilizing cross-talk between morphogenesis-related signaling pathways

利用形态发生相关信号通路之间的串扰开发结直肠癌治疗策略

基本信息

批准号：
18591468
负责人：
NOSHIRO Hirokazu
金额：
$ 2.48万
依托单位：
Kyushu University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2006
资助国家：
日本
起止时间：
2006 至 2007
项目状态：
已结题

项目摘要

Based on our hypothesis " Wnt pathway and hedgehog (Hh) pathwaysuppress each other in colorectal cancel", our research aim is to develop a new therapeutic strategy that targets corosstalk between morphogenesis signaling pathways.During this research period, following data were obtained.1) Evaluation of activation status of Wnt pathway and Hh pathway in colorectal cancer specimens: Nuclear accumulation of b-catenin (Wnt pathway activation) and the Glil staining (BE pathway activation) level were inversely associated in the 40 colorectal cancers (P=0.014).2) Crosstalk between Wnt pathway and Hh pathway in colorectal cancer cells: Suppression of Wnt pathway by Gill transfection in colorectal cancer cells was confirmed by lucrferase assay, western blot analysis, and immunostaining.3) Mechanisms of crosstalk between Wnt pathway and BE pathway:Suppression of Wnt pathway activation in Glil transfected cells was observed even in cells having mutated b-catenin.4) BE pathway activation therapy for colorectal cancers involving Wnt pathway activation: Suppression of proliferation in Wnt pathway-activationg colorectal cancer cells by Glil transfection was confirmed by colony formation assay and three-dimensional culture system.5) Crosstalk between Wnt pathway and BE pathway in other cancers: Crosstalk between Wnt pathway and Hh pathway was also observed in gastric cancer specimens.Most of these data have been published in a form of peer-review manuscript.

基于我们的假设“Wnt通路和Hedgehog（Hh）通路在结直肠取消中相互抑制”，我们的研究目标是开发一种针对形态发生信号通路之间的共茎的新治疗策略。在本研究期间，获得了以下数据。1）评估结直肠癌标本中Wnt通路和Hh通路的激活状态：B-连环蛋白的核积聚（Wnt途径活化）和Glil染色（BE途径激活）水平在40例结直肠癌中呈负相关，（P=0.014）。2）结直肠癌细胞中Wnt途径和Hh途径之间的串扰：通过荧光素酶测定、蛋白质印迹分析和免疫染色证实Gill转染在结直肠癌细胞中对Wnt通路的抑制。3）Wnt通路和BE通路之间的串扰机制：甚至在具有突变的b-连环蛋白的细胞中也观察到Glil转染的细胞中Wnt途径活化的抑制。4）用于涉及Wnt途径活化的结肠直肠癌的BE途径活化疗法：通过集落形成试验和三次细胞凋亡试验证实了Glil转染对Wnt通路激活的结直肠癌细胞增殖的抑制作用。5）其他癌症中Wnt通路与BE通路之间的串扰：在胃癌标本中也观察到Wnt通路与Hh通路之间的串扰，这些数据大多以同行评议手稿的形式发表。