| 陈亦龙,李 维,苏雪萍.抑制自噬通过促进Caspase依赖性细胞凋亡逆转鼻咽癌紫杉醇耐药性的研究[J].中国肿瘤,2018,27(8):626-633. |
| 抑制自噬通过促进Caspase依赖性细胞凋亡逆转鼻咽癌紫杉醇耐药性的研究 |
| Inhibition of Autophagy Sensitizes Taxol-resistant Nasopharyngeal Carcinoma Cells to Taxol Treatment by Enhancing Taxol-induced Caspase-dependent Apoptosis |
| 投稿时间：2018-02-28 |
| DOI：10.11735/j.issn.1004-0242.2018.08.A012 |
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| 中文关键词: 鼻咽肿瘤 紫杉醇 自噬 凋亡 耐药 |
| 英文关键词:nasopharyngeal carcinoma taxol autophagy apoptosis chemoresistance |
| 基金项目:国家自然科学基金青年项目（81702706） |
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| 摘要点击次数: 1892 |
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| 中文摘要: |
| 摘 要：［目的］ 探讨细胞自噬在鼻咽癌紫杉醇耐药中的作用及其机制。［方法］ 以鼻咽癌亲本细胞和紫杉醇耐药细胞为研究对象。自噬抑制剂3-MA抑制自噬，siRNA下调自噬蛋白Beclin-1的表达，分别应用集落形成实验检测细胞的增殖能力，流式细胞术检测凋亡水平，蛋白印迹分析检测自噬相关蛋白和Caspase蛋白的表达水平，透射电子显微镜和荧光显微镜进行细胞形态学观察。通过基因芯片技术分析Caspase家族基因在亲本和耐药细胞中的不同表达。［结果］ 紫杉醇耐药细胞中自噬蛋白Beclin-1、LC3-Ⅱ的表达水平高于亲本细胞（P<0.05）。用自噬抑制剂3-MA预处理鼻咽癌耐药细胞后，CNE-1/Taxol+3-MA和HNE-2/Taxol+3-MA细胞的IC50值分别为(6.25±1.0)nmol/L、(2.19±0.19)nmol/L，与对照组相比，细胞的生长抑制率明显增加（P<0.01）。鼻咽癌紫杉醇耐药细胞转染Beclin-1-siRNA后，CNE-1/Taxol细胞和HNE-2/Taxol细胞的IC50值分别为(5.69±1.23)nmol/L、(3.08±0.67)nmol/L，转染后的细胞对紫杉醇的敏感性明显高于阴性对照组。通过3-MA和Beclin-1-siRNA抑制自噬能增加紫杉醇诱导的Caspase依赖的细胞凋亡，同时能部分逆转鼻咽癌细胞紫杉醇耐药。［结论］ 紫杉醇诱导的鼻咽癌细胞自噬可能是通过降低Caspase依赖的细胞凋亡，从而部分参与了紫杉醇耐药，抑制自噬能通过促进凋亡从而增加鼻咽癌细胞对紫杉醇的敏感性。 |
| 英文摘要: |
| Abstract：［Purpose］ To investigate the effects and mechanisms of autophagy in the taxol resistance of nasopharyngeal carcinoma (NPC) cells.［Methods］ The NPC parental (CNE-1， HNE-2) and taxol-resistant (CNE-1/Taxol， HNE-2/Taxol) cells were used in the study；3-MA was used as autophagy inhibitors；siRNA to Beclin-1 was used to inhibit expression of Beclin-1. Colony formation assay was utilized to detect cell proliferation；flow cytometry assay was used to detect apoptosis. Expression of autophagy-related protein and cleaved Caspase 3 were measured by Western blot analysis. Morphology studies were performed using transmission electron microscopy and fluorescent microscopy. The cDNA microarray was used to analyze the different expression levels of caspase family genes between parental and taxol-resistant cells. ［Results］ The expression levels of autophagy protein Beclin-1， LC3-Ⅱ in taxol-resistant cells were higher than those in parental cells(P<0.05). The IC50 values of taxol in CNE-1/Taxol and HNE-2/Taxol were (6.25±1.0)nmol/L and (2.19±0.19)nmol/L after pretreatment with 3-MA， which were significantly lower than that in control groups(P<0.01).The IC50 value of taxol in CNE-1/Taxol and HNE-2/Taxol were (5.69±1.23)nmol/L and (3.08±0.67)nmol/L after transfection with Beclin-1-siRNA， which were significantly lower than those in control groups(P<0.05) . Inhibition of autophagy through 3-MA and Beclin-1-siRNA enhanced taxol-induced caspase-dependent apoptosis， resulted in partial reversal of the acquired taxol resistance in taxol-resistant cells. ［Conclusion］ The taxol-induced autophagy may protect nasopharyngeal carcinoma cells from caspase-dependent apoptotic death， and inhibition of autophagy can increase the taxol sensitivity by increasing apoptosis. |
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