沉默STAT3增强SNX-2112诱导食管癌干细胞凋亡的研究
DOI: 10.3971/j.issn.1000-8578.2019.18.1004
Keywords: STAT3,热休克蛋白90,SNX-2112,食管癌干细胞,Adriamycin Induced Chemoresistance of Human TNBC MDA-MB-468 Cells Through Stat3-cMyc Signal Pathway,Chordoma Signaling Pathways and Molecular Targeted Therapy,Bergapten Induces Apoptosis of Nasopharyngeal Carcinoma Cells,Norcantharidin Induced Apoptosis of Human Colon Carcinoma Cells LS-174T through#br# Inhibiting JAK-STAT3 Signal Pathway,Gene Expression and Signifi cance of JAK-STAT and ras-MAPK Signaling Pathways#br# in Gastric Cancer Cells,STAT3 signaling pathway in drug resistance,Effect of Silencing STAT3 by siRNA on Expression of MMP-2 in Esophageal Carcinoma Cell Line EC-1,Effects of STAT3 Antisense Oligonucleotide on Proliferation and Apoptosis of MCF-7 Breast Cancer Cells,Expressions of JAK1, p-STAT3 and bcl-2 in Gastric Cancer and Their Significance,Inhibitory Effect of Silencing STAT3 Gene by shRNA on Growth of Xenografted Human Esophageal Carcinoma Cell Line EC1 in Nude Mice,Expression of Stat3 and Correlative Factor and Its Significance in Carcinogenesis of Sporadic Colorectal Tubular Adenoma,Cross-talking between JAK/STAT3 and MAPK/ERK Signaling Transduction Pathways on Invasion and Metastasis of The Human Breast Cancer Cells,Expression of STAT3 Protein in Human Laryngeal Carcinoma and Its Significance,Inhibition of Novobiocin on Proliferation of K562 Cells Involves Disruption Hsp90 Chaperon Function
Abstract:
摘要 目的 通过沉默STAT3探讨Hsp90抑制剂SNX-2112对食管癌干细胞的凋亡诱导效果。方法 构建干扰STAT3的慢病毒载体shSTAT3并转染食管癌干细胞，同时设计阴性对照组，SNX-2112作用于细胞，CCK8法分析shSTAT3与SNX-2112联用对食管癌干细胞的活性抑制效果；软琼脂平板克隆实验研究二者联用对细胞的增殖抑制效果；流式细胞仪检测并分析二者联用对食管癌干细胞的凋亡诱导效果；Western blot分析凋亡蛋白变化。结果 设计并构建的针对STAT3的慢病毒载体shSTAT3能在蛋白（P<0.01）及mRNA水平（P<0.05）有效干扰其表达；经过shSTAT3及0.015625、0.03125、0.0625、0.125、0.25、0.5和1.0 μmol/L的SNX-2112作用24 h后，细胞活性较单用组明显下降（P<0.05），同时SNX-2112的IC50为（0.28±0.01）μmol/L；克隆形成实验显示，二者联用导致细胞克隆形成效率明显下降（P<0.01）；流式细胞仪结果显示，二者联用后细胞凋亡比例以及subG1比例细胞数量显著提高（P<0.01, P<0.01）；Western blot结果显示，shSTAT3及SNX-2112联用后抗凋亡蛋白Bcl2表达水平下调（P<0.05），促凋亡蛋白Bax水平上调（P<0.05）。结论 沉默STAT3增强了Hsp90抑制剂SNX-2112诱导食管癌干细胞凋亡的效果
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