| 陈 坤,雷 杰,张志培,孙 盈,田 丰,李小飞,王小平.FGFR1通过调控PI3K/AKT/mTOR信号通路介导非小细胞肺癌对吉非替尼的耐药[J].,2019,19(2):236-243 |
| FGFR1通过调控PI3K/AKT/mTOR信号通路介导非小细胞肺癌对吉非替尼的耐药 |
| FGFR1 Mediates the Resistance of Non-small Cell Lung Cancer to Gefitinib by Activating PI3K/AKT/mTOR Signaling Pathway |
| 投稿时间：2018-07-02 修订日期：2018-08-07 |
| DOI：10.13241/j.cnki.pmb.2019.02.008 |
| 中文关键词: 非小细胞肺癌 纤维细胞生长因子受体1 PI3K/AKT/mTOR信号通路 吉非替尼 耐药机制 |
| 英文关键词: NSCLC FGFR1 PI3K/AKT/mTOR signaling pathway Gefitinib Resistance mechanisms |
| 基金项目:陕西省自然科学基金项目(2016JM8009) |
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| 中文摘要: |
| 摘要 目的：探讨成纤维细胞生长因子受体1（FGFR1）诱导非小细胞肺癌（NSCLC）吉非替尼获得性耐药的机制。方法：用吉非替尼诱导PC9细胞构建耐药细胞株PC9/GR，用CCK-8、平板克隆形成、transwell技术检测细胞的增殖和迁移能力，用流式细胞术检测细胞的凋亡状况，qRT-PCR、免疫荧光和蛋白免疫印迹技术检测基因表达水平。进一步采用FGFR1抑制剂PD173074或siRNA- FGFR1处理PC9/GR细胞，检测细胞的增殖、迁移、克隆形成能力的变化及Akt、p-Akt、mTOR和p-mTOR表达的变化。结果：PC9/GR细胞的增殖、迁移及对吉非替尼的耐受能力显著增强；FGFR1在PC9/GR细胞中的表达水平显著升高；用PD173074处理PC9细胞后，其增殖、迁移能力及对吉非替尼的耐受能力显著下降；敲低FGFR1后Akt和mTOR的磷酸化水平显著下降。结论：FGFR1通过PI3K/AKT/mTOR信号通路介导非小细胞肺癌对吉非替尼的耐药。 |
| 英文摘要: |
| ABSTRACT Objective: To explore the mechanism of fibroblast growth factor receptor 1 (FGFR1) in inducing NSCLC resistance to gefitinib. Methods: Continuous induction of PC9 cells by gefitinib to construct PC9/GR cell lines. CCK-8 assay and plate clone formation were used to evaluate the growth of the cell. Cells migration ability was assesses through transwell experiment. Annexin V/PI staining and flow cytometry were employed for the detection of apoptosis. QRT-PCR assay was used to detect the mRNA expression levels of the target genes, and immunofluorescence assay and western blotting were used to detect the protein expression levels of the target genes. Results: The proliferation, migration and gefitinib tolerance ability of PC9/GR cells were significantly enhanced. The expression level of FGFR1 in PC9/GR was significantly higher than that in PC9 cells. PD173074 treatment of PC9 cells significantly suppressed its prolifera- tion, migration and gefitinib tolerance ability. Knocking down FGFR1 resulted in a significant decrease in Akt and mTOR phosphoryla- tion levels. Conclusion: FGFR1 mediates the resistance of non-small cell lung(NSCLC) to gefitinib through the PI3K/AKT/mTOR signal- ing pathway. |
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