Cyclopamine decreased the expression of Sonic Hedgehog and its downstream genes in colon cancer stem cells.
Cyclopamine decreased the expression of Sonic Hedgehog and its downstream genes in colon cancer stem cells.
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发表时间：
2014-11
影响因子：
2
通讯作者：
Bat-Erdene Batsaikhan;K. Yoshikawa;N. Kurita;T. Iwata;C. Takasu;H. Kashihara;M. Shimada
中科院分区：
文献类型：
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作者：
Bat-Erdene Batsaikhan;K. Yoshikawa;N. Kurita;T. Iwata;C. Takasu;H. Kashihara;M. Shimada
未标记背景：包括结肠癌在内的大多数实体癌被认为是由癌症干细胞（CSC）引发和维持的，这些癌症干细胞负责治疗抗性，导致肿瘤复发。本研究的目的是阐明Sonic Hedgehog（Shh）信号通路在肿瘤干细胞调控中的可能作用。材料与方法HCT-116细胞系在RPMI-1640培养基中与胎牛血清一起培养，其球体在无血清非贴壁培养中生长。通过定量实时聚合酶链反应（qRT-PCR）分析了用和不用环巴胺处理的细胞的基因表达。结果HCT-116球源性细胞在无血清、非贴壁培养中生长，与在常规培养中生长的亲本细胞相比，显示干细胞标志物、Shh下游基因和上皮-间充质转化（EMT）标志物的表达显著增加。干细胞标记物、Shh下游基因和EMT标记物的表达在癌球中高于亲本细胞系，并且通过环巴胺处理以剂量依赖性方式下调。结论环巴胺处理可下调HCT-116微球上干性标志物、shh下游基因和EMT标志物的表达。
UNLABELLED Backround: Most solid cancers including colon cancer are believed to be initiated from and maintained by cancer stem cells (CSCs), that are responsible for treatment resistance, resulting in tumor relapse. The aim of this study was to clarify the possible role of the Sonic Hedgehog (Shh) signaling pathway in the regulation of cancer stem cells. MATERIALS AND METHODS The HCT-116 cell line was cultured with fetal bovine serum in RPMI-1640 medium and its sphere was grown in serum-free non-adherent culture. Gene expressions were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR) from cells treated with and without cyclopamine. RESULTS HCT-116 sphere-derived cells grown in serum-free, non-adherent culture, showed significantly increased expression of stem cell markers, Shh downstream genes and epithelial-mesenchymal transition (EMT) markers compared to parental cells grown in conventional culture. The expression of stemness markers, Shh downstream genes and EMT markers were higher in cancer spheres than the parental cell line and down-regulated by cyclopamine treatment in a dose-dependent manner. CONCLUSION Overall, these findings show that cyclopamine treatment could down-regulate the expression of stemness markers, shh downstream genes and EMT markers on HCT-116 spheres.