| 范小良,张 健,余泽锋.日柏醇通过内质网应激途径诱导软骨肉瘤细胞凋亡的体外研究[J].肿瘤学杂志,2016,22(12):1020-1025. |
| 日柏醇通过内质网应激途径诱导软骨肉瘤细胞凋亡的体外研究 |
| Hinokitiol Induces Chondrosarcoma Cell Apoptosis Through Endoplasmic Reticulum Stress Pathway |
| 投稿时间：2016-09-01 |
| DOI：10.11735/j.issn.1671-170X.2016.12.B008 |
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| 中文关键词: 日柏醇 软骨肉瘤 内质网应激 细胞凋亡 |
| 英文关键词:Hinokitiol chondrosarcoma endoplasmic reticulum stress apoptosis |
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| 中文摘要: |
| 摘 要：［目的］ 探索日柏醇体外杀伤软骨肉瘤细胞系SW1353的疗效及可能涉及的作用机制。［方法］ 不同浓度日柏醇处理软骨肉瘤细胞后，根据MTS实验绘制细胞杀伤曲线；以Hoechst染色观察细胞凋亡细胞核形态改变。流式细胞术行凋亡双染检测明确凋亡分布情况。通过装载ER Tracker探针荧光显微镜下观察内质网应激状态下细胞内质网肿胀情况。透射电镜观察细胞内质网肿胀的亚显微结构。Western blot分析内质网应激及凋亡相关蛋白表达的改变。通过应用内质网选择性通路抑制剂Salubrinal反向验证PERK-eIF2α信号通路在治疗中所起作用。［结果］ 日柏醇体外诱导软骨肉瘤细胞凋亡，并且呈浓度梯度及时间梯度依赖。日柏醇诱导软骨肉瘤细胞发生内质网应激，出现内质网肿胀。Western blot检测到内质网应激时PERK-eIF2α相关信号通路分子蛋白表达改变，活化Caspase cascade级联反应，活化凋亡效应蛋白cleaved PARP，诱导细胞发生凋亡。使用eIF2α选择性抑制剂能明显阻断日柏醇诱导软骨肉瘤细胞凋亡作用。［结论］ 日柏醇在体外诱导软骨肉瘤细胞发生内质网应激，激活未折叠蛋白反应，进而通过激活PERK-eIF2α信号通路，最终启动Caspase cascade级联反应，诱导软骨肉瘤细胞凋亡。 |
| 英文摘要: |
| Abstract：［Objective］ To investigate the effect of Hinokitiol on apoptosis of chondrosarcoma SW1353 cells and its mechanisms. ［Methods］ The chondrosarcoma SW1353 cells were treated with Hinokitiol at different concentrations（25，50，100μmol/L）for different times (24，48，72h). SW1353 cell proliferation was determined by MTS assay after Hinokitiol treatment；the apoptotic morphology was observed with Hoechst staining and light microscope；the proportion of apoptotic cells was measured by flow cytometry with PE/7-AAD staining. The specificity endoplasmic reticulum (ER) tracker probe was used to demonstrate the edema of ER；the submicrostructure of edema of ER was observed by transmission electron microscope. Salubrinal(SAL) was used to verify the PERK-eIF2α pathway in SW1353 cell apoptosis induced by Hinokitiol. ［Results］ Hinokitiol treatment induced the chondrosarcoma cell apoptosis through ER stress in a concentration-dependent and time-dependent manner. PERK-eIF2α pathway associated proteins were changed when ER stress occurred. Inhibitor of eIF2α blocked the apoptosis induced by Hinokitiol. ［Conclusion］ Hinokitiol can induce ER stress of chondrosarcoma cells，activate the PERK-eIF2α pathway，promote Caspase cascade reaction，resulting in cell apoptosis. |
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