摘要
目的:探讨中药单体异甘草素(isoliquiritigenin,ISL)对人食管鳞癌细胞系EC9706和KYSE450的影响及其作用机制。方法:利用四甲基偶氮唑盐(MTT)法检测ISL对上述2株人食管鳞癌细胞系的细胞毒性;流式细胞术分析ISL对细胞周期及凋亡的影响;Western-blotting技术分析IGF1/IGF-1R信号通路相关蛋白表达以了解ISL的可能作用机制。结果:MTT实验结果表明,ISL以剂量依赖性的方式抑制食管鳞癌细胞EC9706和KYSE450的增殖,IC_(50)值分别为25.56μmol/L和27.78μmol/L。此外,ISL可将2株细胞周期阻滞在G_2/M期及以剂量依赖性的方式诱导细胞发生凋亡,并且显著下调IGF-1R表达及抑制其下游PI3K/AKT和RAS/MAPK信号通路的激活。结论:ISL具有很强的抗食管癌活性,其作用机制与其调节细胞周期和促使细胞凋亡有关。本研究首次证明中药单体ISL具有抗食管癌活性,为临床运用中药治疗食管癌提供了新思路。
Objective:To explore the activity and mechanism of Chinese medicine monomer isoliquiritigenin (ISL) on human esophageal squamous cell carcinoma cell line (ESCC) EC9706 and KYSE450.Methods:Methylthiazolyldiphenyl-tetrazolium bromide (MTT) assay was used to detect the cytotoxicity of ISL on EC9706 and KYSE450.The effects of ISL on cell cycle and cell apoptosis were performed by flow cytometry (FCM).In order to illuminate the mechanism of ISL cytotoxic effects,Western-blotting was used for analyzing the expression of key molecules in the IGF1/IGF-1R signaling pathway.Results:The result of MTT assay suggested that ISL could inhibit the proliferation of EC9706 and and KYSE450 in a dose-dependent manner,with an IC50 value of 25.56 μmol/L and 27.78 μmol/L,respectively. In addition,the data of flow cytometry indicated that ISL caused a significant G2/M arrest and significantly induced apoptosis in both cell lines.Western-blotting confirmed that ISL could down-regulate the expression of IGF-1R and inhibit its downstream PI3K/AKT and RAS/MAPK signal transduction pathway activated.Conclusion:ISL showed high anti-tumor efficacy against esophageal cancer cell lines.It's the first report to show the effects of ISL on esophageal cancer,which provides its potential on the esophageal carcinoma therapy in the future.
出处
《现代肿瘤医学》
CAS
2018年第7期1012-1015,共4页
Journal of Modern Oncology
关键词
异甘草素
食管癌
细胞周期
细胞凋亡
isoliquiritigenin
esophagus cancer
cell cycle
cell apoptosis