姜黄素调控Notch信号通路对肺癌干细胞增殖及凋亡的影响

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。

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

Objective:To explore the effect of curcumin on the proliferation and apoptosis of lung cancer stem cell.Methods:The surface markers（ALDH1) and lung cancer stem cells by using the immune magnetic beads were isolated from lung cancer A549 cell line.The effect of curcumin on the proliferation of lung cancer stem cell was determined by MTT test.Flow cytometry instrument was used to detect the influence curcumin on the apoptosis of lung cancer stem cell.Western blot was used to detect the expression levels of Notch1 and Hes1.Gamma secretase inhibitors inhibit the Notch signaling pathway in lung cancer stem cell proliferation and apoptosis.Research the effects of Gamma secretase inhibitors on the proliferation and apoptosis of lung cancer stem cell by inhibitting the Notch signaling pathway.Results:The ALDH1+ lung cancer stem cells were sorted out from the lung cancer A549 cell line by using immune magnetic bead separation method.The results of MTT test show that the curcumin can inhibit the proliferation of lung cancer stem cell by concentration dependence.After the treatment of curcumin in lung cancer stem cells,the apoptosis rate increased significantly,and the protein expression levels of Notch1 and Hes1 decreased obviously,compared with control group.After the treatment of gamma secretase inhibitors in lung cancer stem cells,the experimental results showed that gamma secretase inhibitors by cutting Notch signaling pathway regulated the protein expression levels of Notch1 and Hes1 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 apoptosis associated with Notch signal pathway.