miRNA-200a调控F0XC1增敏肺癌EGFR-TKI治疗的研究

发布时间：2018-07-16 14:22

【摘要】：目的:探究 miRNA-200a 在非小细胞肺癌(non-small-cell lung cancer,NSCLC)中对靶向治疗疗效的影响及其可能的调控机制。方法:通过RT-PCR、Western blot等方法检测NSCLC细胞中miRNA-200a、FOXC1的表达量;四甲基偶氮唑盐(MTT)实验、细胞划痕实验、Transwell实验分别检测miRNA-200a、FOXC1对肺腺癌细胞生长、迁移、侵袭的影响;荧光素酶报告实验分析FOXC1与miRNA-200a的靶向关系。结果:高表达的miR-200a抑制肺腺癌细胞的生长、上皮-间质转化、迁移、侵袭,并且增加肺腺癌细胞对吉非替尼的敏感性。此外,敲低FOXC1同样可以抑制细胞生长,恢复肺腺癌细胞对吉非替尼敏感性。结论:上调miR-200a或下调FOXC1可以增强NSCLC细胞对吉非替尼的敏感性。这项研究可能提供了一种新的有效的治疗方法来克服表皮生长因子受体-酪氨酸激酶抑制剂(epidermal growth factor receptor tyrosine kinase inhibitors,EGFR-TKIs)治疗的耐药性。
[Abstract]:Aim: to investigate the effect of miRNA-200a on the therapeutic efficacy of non-small-cell lung cancer-NSCLC and its possible regulatory mechanism. Methods: the expression of miRNA-200aFXC1 in NSCLC cells was detected by RT-PCR- Western blot, and the effects of miRNA-200aFOXC1 on the growth, migration and invasion of lung adenocarcinoma cells were detected by MTT assay and cell scratch test. Luciferase report was used to analyze the targeting relationship between FOXC1 and miRNA-200a. Results: the overexpression of miR-200a inhibited the growth, epithelial-interstitial transformation, migration and invasion of lung adenocarcinoma cells, and increased the sensitivity of lung adenocarcinoma cells to gefitinib. In addition, knocking down FOXC1 also inhibited cell growth and restored the sensitivity of lung adenocarcinoma to gefitinib. Conclusion: upregulation of miR-200a or down-regulation of FOXC1 can enhance the sensitivity of NSCLC cells to gefitinib. This study may provide a new and effective treatment to overcome the resistance of epidermal growth factor receptor-tyrosine kinase inhibitor (epidermal growth factor receptor tyrosine kinase inhibitors EGFR-TKIs.
【学位授予单位】：南京医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R734.2

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