当前的研究表明肿瘤干细胞的存在是肿瘤发生、发展、转移和耐药的根本原因，这改变了对传统肿瘤理论的认识。经典的NOTCH信号通路已经被发现在调控血液系统、皮肤、神经系统和乳腺肿瘤的干细胞中发挥着作用。然而，对于该通路如何调控结肠癌干细胞的耐药机制仍不清楚。本课题组前期实验通过细胞系无血清培养获得稳定的结肠癌干细胞球为基础，证实NOTCH通路在结肠癌干细胞中异常激活，并与结肠癌干细胞的形成及其耐药机制密切相关。同时我们前期的实验也发现NOTCH通路、AKT通路和ABCG2化疗抵抗通路之间的关联性。基于本课题组前期实验结果和该领域的相关报道，我们推测在结肠肿瘤干细胞的耐药机制中可能存在NOTCH-AKT-ABCG2这一新的调控网络。本研究拟从细胞、裸鼠模型、临床样本三方面检验该假设，明确该通路在结肠癌耐药中的调控机制，为抗结肠癌耐药提供新的治疗靶点，具有十分重要的理论意义和潜在的临床应用价值。

Drug resistance of tumor stem cells is an important mechanism of chemotherapy failure, this changed the traditional view of chemotherapy. Signal pathway has been found to play a role in the regulation of blood system, nervous system, skin and breast cancer CSCs. However, mechanisms that how these pathways regulate colon cancer stem cell resistance are still unclear. Our preliminary experiment demonstrated that NOTCH pathway is activated in the colon cancer stem cells, and is closely related to the colon cancer stem cell formation and resistance. Based on our previous experimental results and the latest research in this field, we speculate that NOTCH-AKT-ABCG2 pathway plays an important role in the regulation of cancer stem cells chemotherapy.This study includes both in vitro and in vivo experiments. This study will provide new therapy target and help to indicate prognosis.