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ABCG2在非小细胞肺癌厄洛替尼耐药中的作用 被引量：3

Role of ABCG2 in erlotinib resistance in non-small-cell lung cancer
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摘要 目的探讨ABCG2在非小细胞肺癌厄洛替尼耐药中的作用。方法厄洛替尼不同浓度(1、5、25μmol/L)处理A549细胞及其获得性耐厄洛替尼细胞(A549/ER)12、24、48 h后,荧光实时定量PCR观察ABCG2 mRNA表达变化,Western blot检测p-AKT、ABCG2蛋白表达变化。PI3K/AKT通路激活剂(IGF-1)和抑制剂(LY294002)分别作用于A549细胞及A549/ER细胞24 h后,荧光实时定量PCR和Western blot方法分别检测ABCG2 mRNA及p-AKT、ABCG2蛋白表达变化。流式细胞仪检测加入IGF-1和LY294002后ABCG2外排作用。结果与未加入厄洛替尼的A549、A549/ER细胞相比,厄洛替尼(1、5、25μmol/L)作用12、24、48 h后,随着剂量的增加和作用时间的延长,ABCG2的表达与p-AKT水平呈正相关。加入IGF-1 24 h后,A549细胞中ABCG2表达量升高,而加入LY294002的A549/ER细胞,ABCG2表达量下降,并且IGF-1作用24 h后ABCG2外排明显增高。LY294002作用24 h后A549/ER细胞ABCG2外排明显降低。结论 ABCG2经由PI3K/AKT信号通路介导非小细胞肺癌中厄洛潜尼耐药,且阻断PI3K/AKT通路可逆转由ABCG2介导的耐药。 Objective To determine the role of ATP-binding cassette sub-family G member 2 （ABCG2） in erlotinib resistance in non-small-cell lung cancer. Methods A549 cells and acquired erlotinib- resistant A549 cells （A549/ER） were separately treated with different concentrations of erlotinib for 12, 24 and 48 h respectively. Real-time PCR and Western blotting were used to observe the changes of ABCG2 expressions at mRNA and protein levels. The activator （IGF-1） and inhibitor （LY294002） of PI3K/AKT pathway were used to treat A549 cells and A549/ER cells for 24 h, respectively. The expression changes of ABCG2 mRNA and p-AKT and ABCG2 were observed by real-time PCR and Western blot analysis. The efflux effect of ABCG2 after IGF-1 and LY294002 treatment was detected by flow cytometry. Results Compared with the A549 and A549/ER cells without erlotinib treatment, after treated by erlotinib （1, 5 and 25 μmol/L） for 12, 24 and 48 h, the expression of ABCG2 and inhibition or activation of PI3K/AKT signaling pathway were positively correlated with the increase of dosage and treatment time. The expression level of ABCG2 was increased in A549 cells treated with IGF-1 for 24 h and decreased in A549/ER cells treated with LY294002. In addition, the efflux effect of ABCG2 was significantly increased after IGF-1 treatment for 24 h and significantly decreased after LY294002 treatment for 24 h. Conclusion ABCG2 mediates erlotinib resistance in non-small-cell lung cancer by PI3K/AKT pathway, and blocking the pathway will reverse the drug resistance.
作者 张靖 马虎 韩静 李雪涛 陈正堂
机构地区 第三军医大学新桥医院全军肿瘤研究所 合肥医学院附属肿瘤医院肿瘤科
出处 《第三军医大学学报》 CAS CSCD 北大核心 2014年第10期987-991,共5页 Journal of Third Military Medical University
基金 国家自然科学基金(81272496) 重庆市自然科学基金(CSTC2012jjB0076)~~
关键词 肺癌 厄洛替尼 P13K AKT ABCG2 lung cancer erlotinib PI3K/AKT ATP-binding cassette sub-family G member 2
分类号 R434.2 [医药卫生—临床医学] R966 [医药卫生—药理学]
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参考文献14

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同被引文献44

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第三军医大学学报
2014年 第10期

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