| 余长云,刘 勇,秦兆冰.Metadherin参与酸性微环境诱导的鼻咽癌紫杉醇耐药[J].肿瘤学杂志,2018,24(6):542-546. |
| Metadherin参与酸性微环境诱导的鼻咽癌紫杉醇耐药 |
| Metadherin Involves in Acidic Extracellular pH-induced Paclitaxel Resistance in Nasopharyngeal Carcinoma |
| 投稿时间：2017-11-30 |
| DOI：10.11735/j.issn.1671-170X.2018.06.B003 |
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| 中文关键词: 酸性微环境 鼻咽肿瘤 异黏蛋白 上皮间质转化 紫杉醇 |
| 英文关键词:acidic extracellular pH nasopharyngeal carcinoma metadherin epithelial-mesenchymal transition paclitaxel |
| 基金项目:国家自然科学基金资助项目（81402232） |
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| 中文摘要: |
| 摘 要：［目的］ 分析异黏蛋白（metadherin，MTDH）在酸性微环境诱导的鼻咽癌紫杉醇耐药中的作用并探讨其相关机制。［方法］ 不同浓度紫杉醇作用于鼻咽癌细胞CNE-2，48h后CCK-8法检测细胞生长抑制率，确定紫杉醇对CNE-2细胞的IC30。分别用pH 7.4、pH 6.8的细胞培养基培养CNE-2细胞，CCK-8法检测IC30浓度紫杉醇下CNE-2细胞生存率；相差显微镜下观察细胞形态改变；RT-qPCR、Western blot检测MTDH及上皮-间质转化（EMT）标志物表达情况；酸性环境下用siRNA沉默MTDH表达后，检测CNE-2细胞对紫杉醇敏感性及EMT标志物表达变化。［结果］ 紫杉醇对CNE-2细胞的IC30为6.167 nmol/L。IC30浓度下，pH 6.8组细胞的生存率为48.46%±4.39%，明显高于pH 7.4组的31.30%± 5.21%（P=0.013）。酸性环境下沉默MTDH表达后，CNE-2对紫杉醇的敏感性增强，IC30浓度下对照组和沉默组的细胞生存率分别为48.70%±2.35% 和32.87%±2.97%（P=0.020）。沉默MTDH表达可逆转酸性引起的E-cadherin下降、Vimentin表达增强。［结论］ 沉默MTDH可逆转酸性微环境诱导的鼻咽癌CNE-2细胞紫杉醇耐药，这一现象与EMT进程逆转密切相关。 |
| 英文摘要: |
| Abstract：［Objective］ To determine the role of metadherin(MTDH) in acidic extracellular pH(pHe)-induced paclitaxel resistance in nasopharyngeal carcinoma(NPC)，and the related mechanism. ［Methods］ Nasopharyngeal carcinoma CNE-2 cells were stimulated with various concentrations of paclitaxel for 48 h，the proliferation inhibition rate was evaluated by the cell counting kit(CCK-8)，and IC30 value of paclitaxel was determined. Then，CNE-2 cells were incubated in normal(pH 7.4) or acidic(pH 6.8) medium，following IC30 paclitaxel stimulation for 48 h，the cell survival rate was evaluated by CCK-8 assay. Cell morphology was observed under phase contrast microscope. The expression of MTDH and epithelial-mesechymal transition(EMT) makers were detected by quantitative real-time reverse transcription-PCR(RT-qPCR) and Western blot. MTDH expression was blocked by small RNA(siRNA) silencing in NPC cells cultured at a pHe of 6.8. Then，the changes of cell sensitivity to paclitaxel and EMT makers were assessed. ［Results］The IC30 value of paclitaxel in CNE-2 cells was 6.167 nmol/L. The cell survival rate of CNE-2 cells cultured in acidic(pH 6.8) medium was significantly higher than that in normal(pH 7.4) medium(48.46%±4.39% vs 31.30%±5.21%，P=0.013). The sensitivity of CNE-2 to paclitaxel was enhanced after MTDH expression was silenced in acid environment，under the IC30 concentration，the cell survival rate in the control group and the silencing group was 48.70%+2.35% and 32.87%+2.97%，respectively(P=0.02). Silencing of MTDH expression also sensitized acidic pHe-induced down-regulation of E-cadherin and up-regulation of Vimentin. ［Conclusion］ Down-regulation of MTDH expression can reverse the acidic pHe-induced paclitaxel resistance in NPC CNE-2 cells，which is closely correlated with MTDH-mediated EMT. |
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