| 张 欢,文 韬,张凯娜.NID1增强人卵巢癌细胞OVCAR-3干细胞特性及分子机制研究[J].中国肿瘤,2018,27(9):701-707. |
| NID1增强人卵巢癌细胞OVCAR-3干细胞特性及分子机制研究 |
| NID1 Enhances Cancer Stem Cell Phenotypes of Ovarian Cancer Cells |
| 投稿时间：2018-04-03 |
| DOI：10.11735/j.issn.1004-0242.2018.09.A012 |
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| 中文关键词: NID1 卵巢癌 上皮—间质转化（EMT） 肿瘤干细胞. |
| 英文关键词:Nidogen-1（NID1） ovarian cancer epithelial-mesenchymal transition（EMT） cancer stem cells |
| 基金项目:国家自然科学基金（81302263）；重庆医科大学大学生科研与创新实验项目（201628） |
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| 中文摘要: |
| 摘 要：［目的］ 探讨NID1对卵巢癌干细胞表型的潜在影响以及NID1与干细胞标志蛋白联合对预后的潜在价值。［方法］ 采用肿瘤干细胞球形成实验、荧光定量RT-PCR和Western blot分别检测稳定过表达外源NID1的OVCAR-3细胞的自我更新能力和卵巢癌干细胞标志物的表达情况。借助生物信息学分析评估NID1在卵巢癌临床样本中与卵巢癌干细胞标志物的相关性及两者联合对预后预测的价值。［结果］ 与空载细胞相比，稳定过表达NID1的OVCAR-3细胞自我更新能力增强（P=0.006），同时伴随着干细胞标志物CD44（P=0.000）和ABCG2（P=0.000）表达水平升高。经ERK/MAPK通路的抑制剂U0126下调ERK1/2的磷酸化水平后，其CD44和ABCG2的水平下降。此外，基于两套卵巢癌表达谱芯片数据的生物信息学分析表明，NID1的表达水平与CD44（P=0.006；P=0.036）、ABCG2（P=0.000；P=0.000）表达水平均显著正相关，而NID1高表达并且携带干细胞表型的卵巢癌患者总体存活时间最短（P=0.026；P=0.000）。［结论］ NID1可能通过激活ERK/MAPK通路诱导卵巢癌细胞出现干细胞特性，NID1与干细胞标志物联合可能具有预后预测意义。 |
| 英文摘要: |
| Abstract：［Purpose］ To investigate the effect of Nidogen-1(NID1) on phenotype of cancer stem cell(CSC) of ovarian cancer cells. ［Methods］ The self-renewal ability of the OVCAR-3 cells and the stable ectopic expression of NID1 were assessed by sphere formation assay，and the expression levels of ovarian CSC markers CD44 and ABCG2 were detected by quantitative RT-PCR and Western blot，respectively. The correlation between NID1 and ovarian CSC markers was examined with bioinformatic analysis，and the prognostic value of these indicators for ovarian cancer was analyzed. ［Results］ NID1-overexpressed OVCAR-3 cells exhibited significantly greater self-renewal ability(P=0.006) and higher level of ovarian CSC markers CD44 and ABCG2，compared with those of the control group(P=0.000). After decreasing of ERK1/2 phosphorylation in these cells treated with an MEK inhibitor U0126，the expressions of ovarian CSC markers were diminished. The bioinformatic analysis for two sets of chip data showed that the expression of NID1 was highly correlated with the expression of ovarian CSC markers CD44(P=0.006，P=0.036) and ABCG2(P=0.000，P=0.000)；and the overall survival time of ovarian cancer patients with higher expression of NID1 and CSC phenotype was significantly shorter than others(P=0.026；P=0.000). ［Conclusion］ NID1 may induce the CSC phenotypes of ovarian cancer by activating ERK/MAPK pathway，and the combination of NID1 with CSC markers may have prognostic value for patients with ovarian cancer |
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