隐丹参酮通过抑制帽子依赖的翻译促进人肺癌细胞A549的凋亡
DOI: 10.3971/j.issn.1000-8578.2016.07.002
Keywords: A Meta-analysis,Effect of GANT61 on Apoptosis of Esophageal Squamous Carcinoma Cells and Its Mechanism,Effect of Rap2a on Invasion and Metastasis of Lung Cancer Cells and Its Related Mechanism,NSCLC的疫苗治疗研究进展,Immune Killing Effect of Silencing TIPE2 Expression on T Lymphocytes Against Lung Adenocarcinoma Cells LA795,Clinical Investigation on Qingfei Mixture Combined with Chemotherapy on Middle and Advanced Non-small Cell Lung Cancer,Effect of Vascular Endothelial Cadherin on Invasion and Metastasis of Non-small Cell Lung Cancer Cells and Related Mechanism,Advances of FGF/FGFR Signaling Pathway in Targeted Therapy for Squamous Cell Lung Cancer,Sulforaphane Suppressed Proliferation of Lung Cancer Stem Cells in vitro,Experiment of Different Administration Sequences of Apatinib and Paclitaxel on Lung Cancer
Abstract:
摘要 目的 探索隐丹参酮对人肺癌细胞A549中帽子依赖翻译的影响及帽子依赖翻译在隐丹参酮促A549细胞凋亡中的作用。方法 免疫印迹实验检测隐丹参酮对A549细胞中mTOR及4EBP1磷酸化的影响，随后通过m7GTP pull down实验检测隐丹参酮对A549细胞中eIF4F蛋白复合物形成的影响，最终通过免疫印迹实验、Annexin V和CCK8法检测敲低4EBP1表达前后隐丹参酮对A549细胞中抗凋亡蛋白Bcl-2表达、细胞凋亡和存活的影响。结果 隐丹参酮以剂量依赖的方式抑制A549细胞中mTOR及4EBP1的磷酸化、eIF4F蛋白复合物的形成和Bcl-2蛋白的表达。细胞凋亡分析发现，对照组中，隐丹参酮显著地诱导了A549细胞的凋亡[（4.68±0.77）% vs. （31.1±4.1）%, P<0.05]，但敲低4EBP1的表达显著抑制了隐丹参酮的促凋亡作用[（31.1±4.1）% vs.（8.85±1.2）%, P<0.05]。CCK8法检测结果发现，隐丹参酮显著抑制了A549细胞的存活[（1±0.09）% vs.（0.43±0.05）%, P<0.05]，但敲低4EBP1的表达拮抗了EMD638683的抑存活作用[（0.43±0.05）vs.（0.87±0.06）, P<0.05]。结论 隐丹参酮通过抑制mTOR激酶的活性抑制4EBP1磷酸化，从而抑制A549细胞中帽子依赖的翻译，进而抑制抗凋亡蛋白Bcl-2的表达诱发人肺癌细胞A549的凋亡
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