摘要
目的探讨青蒿素对结直肠癌细胞放疗敏感性的影响及其机制。方法采用克隆形成试验,评估青蒿素结合放射线对人类结直肠癌细胞株Lovo细胞的生长影响,利用脱氧核糖核酸片段试验分析青蒿素是否会促进放射线诱导Lovo细胞的凋亡,并运用蛋白质免疫印迹法确认青蒿素对放射线活化核转录因子-κβ(NF-κB)及其所调控的抗凋亡蛋白的影响。结果青蒿素可以显著增加放射线对Lovo细胞的抑制作用,通过增加Lovo的线粒体和非线粒体的凋亡路径,强化放射线诱导细胞凋亡的发生。蛋白质免疫印迹法结果显示,青蒿素会减少放射线活化Lovo细胞内NF-κβ活性和受NF-κβ调控的抗凋亡蛋白B-细胞淋巴瘤基因2(Bcl-2)和转换酶抑制蛋白(C-FLIP)等的表达;进一步,因NF-κβ的活性受到抑制会造成Lovo细胞对放射线变得更敏感,因此,证实青蒿素是结直肠癌细胞株的辐射敏感剂。结论青蒿素通过抑制NF-κβ活性,增强结直肠癌细胞的放疗敏感性。
【Objective】To investigate whether artemisinin is able to radiosensitize colorectal cancer cells through suppression of radiation-induced NF-κβ activity.【Methods】The effects of artemisinin combined with radiation on cell proliferation in Lovo cells were evaluated with clonogenic formation assay. Whether artemisinin can increase radiation-induced apoptosis was investigated using DNA fragmentation assay. We also determined the effects of artemisinin on radiation-induced NF-κβ activity and increased the expression of NF-κβ regulated gene products with western blotting assay. To confirm whether NF-κβ inhibition can sensitize colorectal cancer to radiation, the effects of NF-κβ inhibitor combined with radiation in Lovo cell were evaluated in this study. 【Results】Artemisinin can significantly increase radiation-inhibited cell proliferation as compared to radiation alone. Artemisinin also enhanced radiation-induced cell apoptosis via dependent and independent mitochondrial pathways. We also found artemisinin decreased radiation activated NF-κβ activity and increased the expression of NF-κβ regulated gene products（Bcl-2 and C-FLIP） from western blotting assay. In addition, the results also showed NF-κβ inhibitor can increase radiosensitivity in Lovo cell.【Conclusion】Artemisinin enhances the radiosensitivity of colorectal cancer cells by inhibiting the activity of NF-κβ.
作者
邓平
陈新文
DENG Ping;CHEN Xinwen(Departmemt of General Surgery,the Cili County People＇s Hospital of Zhangjiajie City,Zhangjiajie,Hunan 427200,China;The 3rd Department of General Surgery,the First People＇s Hospital of Changde City,Changde,Hunan415003,China)
出处
《中国医学工程》
2018年第8期14-19,共6页
China Medical Engineering
