【摘要】 [目的]通过实验研究观察千金藤素(Cepharanthine,CEP)对人结肠癌的抗增殖作用。[方法]本研究通过活体荧光示踪技术研究CEP对人结肠癌细胞HCT116裸鼠异体移植肿瘤模型的抗结肠癌作用,运用报告基因技术研究CEP对肿瘤相关的8条信号通路活化程度的影响,采用流式细胞仪测定CEP对细胞周期分布的影响。[结果]CEP体外能抑制多种人源肿瘤细胞的增殖,IC50范围为0.8-11.5μM。CEP能使HCT116细胞的S期和G2/M期百分比明显增加。通过对MAPK/ERK、MAPK/JNK、Wnt、Notch、Cell Cycle/pRb-E2F、NFκB、Myc/Max以及Hypoxia等8条信号通路报告基因活化程度的研究,发现CEP主要通过抑制MAPK/ERK和NFκB信号通路起到抑制肿瘤增殖的作用。动物模型的实验结果显示,CEP能抑制肿瘤增殖,促进肿瘤组织坏死。[结论]CEP通过抑制MAPK/ERK和NFκB信号通路的活化抑制人结肠癌细胞HCT116裸鼠异体移植肿瘤的增殖。更多还原

【Abstract】 [Objective]To investigate the anti-proliferative effects of CEP on HCT116 cells and in mouse xenograft model. [Methods]The in vivo anti-cancer activity of CEP was determined with Xenogen bioluminescence imaging in a xenograft tumor model. The cell-based multiple signaling pathway reporter assays were carried out to determine the effects of CEP on these pathways. [Results] CEP inhibited growth of human cancer cells, the IC50was0.8~11.5 μM. CEP induced cell cycle arrest in S and G2/M phase. CEP also inhibited xenograft tumor growth in athymic nude mice bearing HCT116cells. The xenograft tumor size was significantly reduced upon the treatment with CEP(10 or 20 mg·kg-1body weight) for up to 3 weeks. Pathway-specific reporter assays indicated that CEP effectively suppressed the NF-κB and MAPK/ERK signaling pathways. [Conclusions] Our results suggest that the anticancer activity of CEP in colon cancer cells may be mediated through targeting NF- κB and MAPK/ERK signaling pathways.更多还原