摘要
目的:研究半枝莲中主要成分野黄芩苷对结肠肿瘤干细胞(CSC)自我更新的影响,并从Hedgehog信号通路阐明其作用机制。方法:从HT-29人结肠腺癌上皮细胞株中分拣出结肠肿瘤干细胞(HT-29CSC),并对其进行无血清悬浮培养。用CCK-8试验研究野黄芩苷对HT-29CSC活性的影响;用干细胞球形成试验研究野黄芩苷对HT-29CSC体外自我更新的影响;用qRT-PCR研究野黄芩苷对结肠肿瘤干细胞标记物基因CD133和增殖基因ki-67表达的影响,和对结肠肿瘤干细胞中Hedgehog信号通路基因Ptch1和Gli1表达的影响。结果:终浓度为40μg/ml、80μg/ml和160μg/ml的野黄芩苷可以浓度依赖性地抑制HT-29CSC体外活性,抑制HT-29CSC体外自我更新,下调结肠肿瘤干细胞标记物基因CD133和增殖基因ki-67 mRNA水平,抑制结肠肿瘤干细胞中Hedgehog信号通路基因Ptch1和Gli1 mRNA转录。结论:野黄芩苷可以抑制结肠肿瘤干细胞活性和自我更新,其机制在于抑制Hedgehog信号通路的活性。
Objective： To investigate the effect of scutellarinon on the self-renewal of colonic cancer stem cells（CSC） and its underlying mechanism through hedgehog signaling pathway. Methods： Colonic cancer stem cells were fractionated from human colonic adenocarcinoma epithelial cells HT-29,named HT-29 CSC. The effect of scutellarin on the cell viability of HT-29 CSC was determined with CCK-8 assay. The function of scutellarinon HT-29 CSC self-renewal was assessed with spheroid formation assay. The effect of scutellarin on expressions of colonic CSC marker gene CD133 and proliferation gene Ki-67,and expressions of Ptch1 and Gli1 involved in hedgehog signaling pathway of colonic CSC were measured by quantitative real-time RT-PCR. Results： Scutellarin at final concentrations of 40μg/ml,80 μg/ml and 160 μg/ml dosedependently inhibited HT-29 CSC viability and its self-renewal,down regulated mRNA levels of CD133 and Ki-67,and decreased mRNA transcriptions of Ptch1 and Gli1 involved in hedgehog signaling pathway of colonic CSC. Conclusions： Scutellarin suppresses colonic CSC selfrenewal by reducing the activity of hedgehog signaling pathway.
出处
《中药药理与临床》
CSCD
北大核心
2017年第5期13-16,共4页
Pharmacology and Clinics of Chinese Materia Medica
基金
国家自然科学基金面上项目(编号:81573813
81173598)
教育部留学回国人员科研启动基金(编号:2013693)
