鸦胆子苦醇对非小细胞肺癌Nrf2-Notch1信号轴的影响机制研究

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摘要目的探讨鸦胆子苦醇在非小细胞肺癌A549、H460细胞增殖中的作用。方法采用四甲基偶氮唑盐（MTT）法检测鸦胆子苦醇对A549、H460细胞的半数抑制浓度（IC50）；Hoechst33258染色，倒置荧光显微镜下观察细胞凋亡的形态学变化；通过CCK-8法检测细胞活力；Annexin-V-FITC/PI双染法检测细胞凋亡；Western blot免疫印迹法检测A549、H460细胞Nrf2、Notch1蛋白表达。结果鸦胆子苦醇处理A549、H460细胞的IC50分别为（0.70±0.03）、（0.47±0.05）μmol/L；流式细胞试验结果显示，鸦胆子苦醇处理后A549、H460细胞凋亡率显著升高，与对照组比较差异均有高度统计学意义（均P ＜ 0.01）；Western blot检测结果显示，鸦胆子苦醇可降低细胞内Nrf2、Notch1的蛋白表达。结论鸦胆子苦醇可以抑制A549、H460细胞的生长，其机制可能与抑制Nrf2-Notch1信号轴有关。

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	王敏刘其礼许帅李品玉李俊涛▲

关键词 ：鸦胆子苦醇, 非小细胞肺癌, Nrf2, Notch1, 细胞生长

Abstract：Objective To explore the effects of Brusatol in the proliferation of A549 and H460 cells of non-small cell lung cancer. Methods The median inhibitory concentration (IC50) of Brusatol for A549 and H460 cells was assessed by methyl thiazolyl tetrazolium (MTT) assay. Through hoechst33258 staining, the morphological changes of cell apoptosis were observed under the inverted fluorescence microscope. The cell viability was detected by CCK-8. The cell apoptosis was tested by Annexin-V-FITC/PI staining. The expression of Nrf2 and Notch1 protein of A549 and H460 cells was measured by Western blot. Results The IC50 of A549 and H460 cells dealt with Brusatol was (0.70±0.03), (0.47±0.05) μmol/L respectively. The results of flow cytometry showed that the apoptosis rates of A549 and H460 cells dealt with Brusatol were increased obviously, which had highly statistically significant differences compared with those of control group (all P ＜ 0.01). The results of Western blot showed that Brusatol could decrease the expression of Nrf2 and Notch1 protein. Conclusion Brusatol can inhibit the growth of A594 and H460 cells, the mechanism may be related to the inhibition of Nrf2-Notch1 axis.

Key words： Brusatol Non-small cell lung cancer Nrf2 Notch1 Cell growth

基金资助:广东省肇庆市科技创新指导类项目（201704031 425）；
肇庆医学高等专科学校“创新强校工程”建设规划一般项目（6-119）。

通讯作者: ▲通讯作者

作者简介: 王敏（1980.11-），女，硕士；研究方向：非小细胞肺癌的治疗及机制研究。

引用本文:

王敏刘其礼许帅李品玉李俊涛▲. 鸦胆子苦醇对非小细胞肺癌Nrf2-Notch1信号轴的影响机制研究[J]. 中国医药导报, 2018, 15(19): 16-19.
WANG Min LIU Qili XU Shuai LI Pinyu LI Juntao▲. Study on the mechanism of the influence of Brusatol for the Nrf2-Notch1 axis of non-small cell lung cancer. 中国医药导报, 2018, 15(19): 16-19.

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http://www.yiyaodaobao.com.cn/CN/ 或 http://www.yiyaodaobao.com.cn/CN/Y2018/V15/I19/16

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