小分子化合物ITE对肺癌H446干细胞增殖的作用及机制研究

Effect and Mechanism of Small Molecule Compounds Named ITE on Proliferation of Human Small Cell Lung Carcinoma Stem Cells H446

目的:探讨小分子化合物ITE对人小细胞肺癌H446干细胞增殖的作用及机制。方法:免疫荧光法检测人肺癌H446干细胞中Oct4蛋白的表达。MTT法测定ITE对肺癌H446干细胞增殖的影响。Western blot法检测ITE对Oct4和Bcl-2蛋白表达的影响。结果:与H446亲本细胞相比,富集干细胞中Oct4的表达明显增加(P<0.05)。与DMSO组相比,ITE呈浓度梯度依赖性地降低H446富集干细胞活力,20μM的ITE处理24h可降低富集干细胞活力至0.46±0.03(P<0.05)。与Control组相比,ITE显著下调富集干细胞中Oct4及Bcl-2蛋白表达(均P<0.05)。结论:小分子化合物ITE可通过下调干细胞转录因子Oct4和凋亡抑制基因Bcl-2,抑制人H446干细胞的增殖。

Objective:To explore the effect and mechanism of small molecule compound named ITE on the proliferation of human small cell lung cancer stem cells H446.Methods:The expression of Oct4 protein in human lung cancer stem cells H446 was detected by immunofluorescence.MTT assay was used to determine the effect of ITE on the proliferation of lung cancer stem cells H446.The protein expression of Oct4 and Bcl-2 were detected by Western blot.Results:Compared with parent H446 cells,the expression of Oct4 in enriched stem cells was significantly increased(P<0.05).Compared with the DMSO group,the activity of enriched stem cells was decreased in a concentration-gradient dependence by ITE,and the cell activity was decreased to 0.46±0.03 by 20μM ITE treatment for 24 h(P<0.05).Compared with the control group,ITE significantly down-regulated the protein expression of Oct4 and Bcl-2 in enriched stem cells(both P<0.05).Conclusion:Small molecule compound named ITE can inhibit the proliferation of human stem cells H446 by downregulating the stem cell transcription factor Oct4 and the apoptotic suppressor gene Bcl-2.