项目名称: 黄芩苷调节上皮间质转化抑制结肠癌干细胞增殖、侵袭的作用与机制研究
项目编号: No.81473679
项目类型: 面上项目
立项/批准年度: 2015
项目学科: 医药、卫生
项目作者: 杨柏霖
作者单位: 南京中医药大学
项目金额: 72万元
中文摘要: 结肠癌肿瘤干细胞是导致结肠癌对放化疗耐药和/或转移复发的根本原因。TGF-β信号通路的激活促使实体瘤干细胞上皮间质转化后获得了增殖、侵袭能力,增加了对化疗药物的耐药性。近年来,阻断肿瘤干细胞上皮间质转化,抑制其增殖、分化和侵袭引起广泛关注。本课题组前期研究证实了黄芩苷能够诱导结肠癌肿瘤细胞凋亡,具有明显抑制结肠癌裸鼠原位移植瘤生长和转移的作用,其机制与下调TGF-β、PCNA、P53等基因表达有关。本研究拟进一步从体外观察黄芩苷干预对结肠癌肿瘤干细胞增殖、分化和侵袭能力的影响,并通过裸鼠原位移植瘤体内实验,使用流式细胞术、荧光定量、免疫印迹等方法,探讨黄芩苷通过TGF-β/Smads信号通路调控上皮间质转化抑制结肠癌干细胞增殖、分化和转移潜能的分子机制,寻找结直肠癌特异性治疗靶点和药物,同时也是对中药有效成分作用机制的新探索。
中文关键词: 结肠癌;黄芩苷;肿瘤干细胞;TGF-β/Smads信号通路;上皮间质转化
英文摘要: The cancer stem cells (CSCs) are the underlying cause of colon cancer to chemotherapy-resistant, metastasis and relapse. Solid tumors stem cells gain self-renewal, aggressive traits and chemoresistance by epithelial to mesenchymal transition (EMT) after TGF-β signaling pathway activation. The inhibition of invasion and metastasis through inhibition of the EMT of CSCs received extensive attention in recent years. The experiments performed by our group have confirmed that Baicalin not only has the ability to induce colon cancer cells apoptosis, but also has a significant inhibitory effect on the growth and metastasis of nude mouse orthotopic xenografts model of colorectal cancer. The mechanism of these actions is related to proteins that down-regulate the expression of TGF-β、PCNA、P53 genes. In this study, flow cytometry, real-time quantitative RT-PCR, Western bloting and other techniques will be used to further observe the effect of Baicalin on the CSCs proliferation, differentiation and invasion ability in vivo and in vitro. The aim of this study is to explore the effect of Baicalin on the TGF-β/Smads pathway and TGF-β-induced EMT as possible molecular mechanisms that mediate self-renewal and differentiation of CSCs. This research will be not only an endeavor to look for new target and drug for colon cancer therapy, but also a new exploration on the effective component of traditional Chinese medicine.
英文关键词: Colon Cancer;Baicalinr;Cancer stem cell;TGF-β/Smads pathway;Epithelial-mesenchymal transition