姜黄素调控Notch信号通路对肺癌干细胞增殖及凋亡的影响  

Effect of curcumin on lung cancer stem cells via Notch signaling pathway

作　　者：杨秦梅 崔青荣[1] 李彬[2] 李宁[3] 周庆伟[1] Yang Qinmei;Cui Qingrong;Li Bin;Li Ning;Zhou Qingwei(Department of Respiration Ⅲ;Department of Respiration Ⅱ;Department of Respiratory Medicine,The First Affiliated Hospital of Henan University of TCM,Henan Zhengzhou 450000,China.)

机构地区：[1]河南中医药大学第一附属医院呼吸三区,河南郑州450000 [2]河南中医药大学第一附属医院呼吸二区,河南郑州450000 [3]河南中医药大学第一附属医院呼吸内科,河南郑州450000

出　　处：《现代肿瘤医学》2018年第20期3199-3204,共6页Journal of Modern Oncology

基　　金：国家自然科学基金青年项目(编号:81501991);河南省高等学校重点科研项目(编号:18A360010)

摘　　要：目的:研究姜黄素对肺癌干细胞增殖及凋亡的影响。方法:利用免疫磁珠标记肺癌表面标记物乙醛脱氢酶1(ALDH1),从肺癌A549细胞系中分离肺癌干细胞; MTT实验检测姜黄素对肺癌干细胞增殖的影响;流式细胞仪检测姜黄素对肺癌干细胞凋亡的影响; Western blot检测Notch1和Hes1蛋白的表达情况;抑制剂γ-分泌酶抑制Notch信号通路研究对肺癌干细胞增殖及凋亡的影响。结果:利用免疫磁珠分选法分选出肺癌细胞系A549中ALDH1+肺癌干细胞。MTT检测结果显示,姜黄素能够呈浓度依赖性的抑制肺癌干细胞的增殖;经姜黄素处理后的肺癌干细胞,与对照组相比,凋亡率明显升高,Notch1和Hes1蛋白的表达明显下降。经γ-分泌酶抑制剂处理肺癌干细胞后,实验结果显示,γ-分泌酶抑制剂通过下调Notch1和Hes1蛋白的表达调控Notch信号通路抑制肺癌干细胞的增殖,诱导其凋亡。结论:姜黄素抑制肺癌干细胞的增殖,诱导其凋亡与Notch信号通路有关。Objective：To explore the effect of curcunfin on the proliferation and apoptosis of lung cancer stem cell. Methods ：The surface markers（ ALDH1 ） and lung cancer stem cells by using the inmmne magnetic beads were isolated from lung cancer A549 cell line. The effect of eureunfin on the proliferation of lung cancer stem cell was de-termined by MTT test. Flow eytometry instrument was used to detect the influence eureunfin on the apoptosis of lung cancer stem cell. Western blot was used to detect the expression levels of Notehl and Hesl. Gamnla seeretase inhibi-tors inhibit the Notch signaling pathway in lung cancer stem cell proliferation and apoptosis. Research the effects of Gamma seeretase inhibitors on the proliferation and apoptosis of lung cancer stem cell by inhibitting the Notch signa ling-pathway. Results ：The ALDH1^＋ lung cancer stem cells were sorted out from the lung cancer A549 cell line by u-sing immune magnetic bead separation method. The results of MTT test show that the eureumin can inhibit the prolif-eration of lung cancer stem cell by concentration dependence. After the treatment of eureumin in lung cancer stem cells,the apoptosis rate increased significantly,and the protein expression levels of Notehl and Hesl decreased obvi-ously,compared with control group. After the treatment of gamma seeretase inhibitors in lung cancer stem cells,the ex-perimental results showed that gamma seeretase inhibitors by cutting Notch signaling pathway-regulated the protein ex-pression levels of Notehl and Hesl and inhibited the proliferation of lung cancer stem cell and induced its apoptosis.Conclusion ： The results suggest that curcumin can inhibit the proliferation of lung cancer stem cell and induce its ap-optosis associated with Notch signal pathway.

关 键 词：姜黄素 NOTCH信号通路 干细胞 增殖 凋亡 

分 类 号：R734.2[医药卫生—肿瘤]