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目的:探讨食管鳞癌细胞中LSD1对Notch信号通路的调控作用及调控机制。方法:Western blot法检测5种食管鳞癌细胞KYSE450、KYSE790、Eca109、EC9706和TE-1中LSD1及Notch通路相关蛋白的表达情况。用LSD1抑制剂TCP处理KYSE450、KYSE790和Eca109细胞或用LSD1 siRNA处理Eca109细胞,Western blot检测处理前后细胞中LSD1、组蛋白H3K4me2和Notch信号通路相关蛋白的表达情况。结果:5种食管鳞癌细胞中均存在LSD1及Notch信号通路相关蛋白的表达,且表达水平不同;TCP处理后,与未处理组相比,KYSE450、KYSE790和Eca109细胞中LSD1的表达水平均降低,组蛋白H3K4me2表达升高,Notch信号通路相关蛋白的表达均降低(P<0.05);LSD1 siRNA同样使Eca109细胞中LSD1与Notch信号通路相关蛋白表达受到抑制(P<0.05)。结论:食管鳞癌细胞中LSD1对Notch信号通路有调节作用,且LSD1可能是通过与Notch靶基因Hes1的启动子区域结合实现的。
Objective: To investigate the regulatory effect of LSD1 on Notch signaling pathway and its regulatory mechanism in esophageal squamous cell carcinoma. Methods: Western blot was used to detect the expression of LSD1 and Notch pathway related proteins in 5 kinds of esophageal squamous cell carcinoma cell lines, KYSE450, KYSE790, Eca109, EC9706 and TE-1. Eca109 cells were treated with LSD1 inhibitor TCP, KYSE790 and Eca109 cells or LSD1 siRNA. The expression of LSD1, histone H3K4me2 and Notch signaling pathway proteins were detected by Western blot. Results: The expressions of LSD1 and Notch signal pathway related proteins were all found in all five esophageal squamous cell carcinomas, and the expression levels of LSD1 in KYSE450, KYSE790 and Eca109 cells were lower than those in untreated group after TCP treatment (P <0.05). The expressions of H3K4me2 and H3protein in Notch signaling pathway were all decreased (P <0.05). LSD1 siRNA also inhibited the expression of LSD1 and Notch signaling pathway in Eca109 cells (P <0.05). CONCLUSION: LSD1 regulates Notch signaling pathway in esophageal squamous carcinoma cells, and LSD1 may be associated with the promoter region of Hes1, a target gene of Notch.