【摘要】：目的:探究 miRNA-200a 在非小細(xì)胞肺癌(non-small-cell lung cancer,NSCLC)中對(duì)靶向治療療效的影響及其可能的調(diào)控機(jī)制。方法:通過RT-PCR、Western blot等方法檢測NSCLC細(xì)胞中miRNA-200a、FOXC1的表達(dá)量;四甲基偶氮唑鹽(MTT)實(shí)驗(yàn)、細(xì)胞劃痕實(shí)驗(yàn)、Transwell實(shí)驗(yàn)分別檢測miRNA-200a、FOXC1對(duì)肺腺癌細(xì)胞生長、遷移、侵襲的影響;熒光素酶報(bào)告實(shí)驗(yàn)分析FOXC1與miRNA-200a的靶向關(guān)系。結(jié)果:高表達(dá)的miR-200a抑制肺腺癌細(xì)胞的生長、上皮-間質(zhì)轉(zhuǎn)化、遷移、侵襲,并且增加肺腺癌細(xì)胞對(duì)吉非替尼的敏感性。此外,敲低FOXC1同樣可以抑制細(xì)胞生長,恢復(fù)肺腺癌細(xì)胞對(duì)吉非替尼敏感性。結(jié)論:上調(diào)miR-200a或下調(diào)FOXC1可以增強(qiáng)NSCLC細(xì)胞對(duì)吉非替尼的敏感性。這項(xiàng)研究可能提供了一種新的有效的治療方法來克服表皮生長因子受體-酪氨酸激酶抑制劑(epidermal growth factor receptor tyrosine kinase inhibitors,EGFR-TKIs)治療的耐藥性。
[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.
【學(xué)位授予單位】：南京醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R734.2

【參考文獻(xiàn)】

相關(guān)期刊論文 前1條

1 Xin An;Cesar Sarmiento;Tao Tan;Hua Zhu;;Regulation of multidrug resistance by microRNAs in anti-cancer therapy[J];Acta Pharmaceutica Sinica B;2017年01期

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本文編號(hào)：2126666