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上调mir-7表达后肺腺癌细胞对吉非替尼敏感性的变化及其机制研究 被引量:2

Change in sensitivity of A549 cells to gefitinib after up-regulation of mir-7 expression and its mechanism
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摘要 目的观察上调人肺腺癌A549细胞中mir-7的表达水平后,细胞对吉非替尼敏感性的变化及其可能机制。方法取对数生长期A549细胞,随机分为对照组(NC组)、转染组(mir-7组)、吉非替尼组(吉非替尼处理细胞,G组)、联合组(转染mir-7后用吉非替尼处理细胞,G+mir-7组)。MTT法检测吉非替尼对A549细胞的半数抑制浓度(IC50),Real-time PCR及Western blotting检测表皮生长因子受体(EGFR)、胰岛素样生长因子受体1(IGF-1R)、Raf1、细胞外信号调节激酶(ERK)的mRNA和蛋白表达水平。结果 G+mir-7组吉非替尼对A549细胞的IC50(8.57±0.61μmol/L)明显低于G组(15.63±0.82μmol/L,P<0.01)。Real-time PCR及Western blotting检测结果显示,G+mir-7组EGFR、IGF-1R、Raf1、ERK的mRNA及蛋白表达水平明显低于mir-7组、G组和NC组(P<0.05)。结论上调mir-7表达可增加肺腺癌细胞对吉非替尼的敏感性,其机制可能与mir-7抑制EGFR及IGF-1R通路有关。 Objective To observe the change in sensitivity of human lung adenocarcinoma A549 cells to gefitinib after up- regulation of mir-7 expression and its underlying mechanism. Methods The logarithmic growth phase A549 cells were harvested and randomly divided into 4 groups: normal control group (NC group), transfection group (mir-7 group), gefitinib group (G group), and G+mir-7 group (A549 cells were treated with gefitinib after mir-7 transfection). The MTT assay was used to determine the 50% inhibitory concentration (IC50) ofgefitinib for A549 cells. Real-time PCR and Western blot were used to determine the mRNA and protein expression of epidermal growth factor receptor (EGFR), insulin-like growth factor 1 receptor (IGF-1R), Rafl and extracellular signal-regulated kinase (ERK). Results The IC50 of gefitinib to A549 cells was significantly lower in G+mir-7 group (8.57 ±0.61μmol/L) than in gefitinib group (15.63 ±0.82μmol/L, P〈0.01). The results of real-time PCR and Western blot showed that the mRNA and protein expressions of EGFR, IGF-1R, Rafl and ERK were significantly lower in G+mir-7 group than in NC group, mir-7 group and gefitinib group (P〈0.01). Conclusion The up-regulation of mir-7 expression may enhance the sensitivity of A549 cells to gefitinib, and its mechanism may be related to the inhibitory effect of mir-7 on signal pathway of EGFR and IGF-1R.
出处 《解放军医学杂志》 CAS CSCD 北大核心 2013年第6期481-484,共4页 Medical Journal of Chinese People's Liberation Army
基金 辽宁省博士科研启动基金(20091108)~~
关键词 非小细胞肺 吉非替尼 微小RNAS carcinoma, non-small-cell lung gefitinib microRNAs
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