| 黄开颜,吕旭阳,周叙强,等.莪术醇下调FoxD2-AS1逆转胶质瘤细胞替莫唑胺化疗耐药的作用研究[J].浙江中医药大学学报,2021,45(4):391-397, 419. |
| 莪术醇下调FoxD2-AS1逆转胶质瘤细胞替莫唑胺化疗耐药的作用研究 |
| Study on the Down-regulation of FoxD2-AS1 by Curcumol in the Treatment of Glioma with Temozolomide Chemotherapy Resistance |
| DOI：10.16466/j.issn1005-5509.2021.04.014 |
| 中文关键词: 胶质瘤 FoxD2-AS1 替莫唑胺耐药 莪术醇 细胞凋亡 抗肿瘤药 基因敲除 细胞周期 |
| 英文关键词: golima FoxD2-AS1 Temozolomide resistance curcumol cell apoptosis anticarcinoma drug gene knockout cell cycle |
| 基金项目:浙江省自然科学基金探索项目(LY20H280005)；浙江省新苗人才计划项目(2019R410036)；国家自然科学基金青年项目(81602624) |
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| 中文摘要: |
| [目的]初步明确长链非编码RNA(long non-coding RNA，lncRNA)FoxD2-AS1与胶质瘤替莫唑胺(Temozolomide，TMZ)耐药的关系，并探索莪术醇逆转胶质瘤替莫唑胺耐药与FoxD2-AS1基因表达的相关性。[方法]以生物信息学分析胶质瘤lncRNA表达谱；以胶质瘤A172、U251细胞系为研究对象，采用药物浓度递增法建立耐药细胞系A172/TMZ、U251/TMZ；以流式细胞术检测干扰FoxD2-AS1对耐药细胞凋亡的影响；莪术醇以不同浓度和时间梯度处理耐药细胞后，以Hoechst染色观察细胞形态变化，实时荧光定量聚合酶链式反应(Real-time quantitative polymerase chain reaction，RT-qPCR)检测不同浓度莪术醇处理后耐药细胞中FoxD2-AS1的表达水平。[结果]lncRNA FoxD2-AS1在胶质瘤患者瘤体组织中高表达，其高表达与患者总生存率呈负相关；敲除FoxD2-AS1可显著增加耐药细胞对TMZ的敏感性并促进细胞凋亡，诱导细胞周期发生S和G2/M期阻滞；莪术醇和TMZ联用显著增加耐药细胞凋亡的典型变化。RT-qPCR结果显示，莪术醇处理后耐药细胞内FoxD2-AS1的含量明显下降，且具有浓度和时间依赖性。[结论]敲除FoxD2-AS1基因可以逆转胶质瘤细胞TMZ耐药。莪术醇可抑制胶质瘤耐药细胞的增殖，并呈时间和剂量依赖性，其作用机制与下调FoxD2-AS1基因表达有关。 |
| 英文摘要: |
| [Objective]To reveal the relationship between the long non-coding RNA(lncRNA) FoxD2-AS1 and Temozolomide(TMZ) resistance of glioma and investigate the correlation between curcumol reversing chemotherapy resistance and FoxD2-AS1 gene expression in glioma. [Methods]The expression profile of lncRNA in glioma was analyzed by bioinformatics. The cell lines A172 and U251 were chosen as the research objects， drug resistant cell lines A172/TMZ and U251/TMZ were established by increasing drug concentration.Flow cytometry analysis was performed to determine the effect of FoxD2-AS1 interference on apoptosis of drug-resistant cells.Hoechst staining was used to observe the morphological changes of drug-resistant cells after treatment with different concentrations and time gradients of curcumol; Real-time quantitative polymerase chain reaction(RT-qPCR) was used to detect FoxD2-AS1 expression in drug-resistant cells treated with curcumol at different concentrations. [Results]lncRNA FoxD2-AS1 was highly expressed in the tumor tissues of glioma patients， and its high expression was negatively correlated with the overall survival rate.FoxD2-AS1 knockout significantly increased the sensitivity of drug-resistant cells to TMZ and promoted cell apoptosis， and arrested cell cycle in S and G2/M phase. The combination of curcumol and TMZ significantly increased the typical changes of apoptosis in drug-resistant cells. The RT-qPCR results showed that the FoxD2-AS1 content in the resistant cells decreased significantly after curcumol treatment in a concentration time dependent manner.[Conclusion]FoxD2-AS1 gene knockout can reverse TMZ resistance of glioma， and curcumol can inhibit the proliferation of glioma resistant cells in a time-dose dependent manner， and the mechanism of action is related to the down-regulation of FOXD2-AS1 gene expression. |
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