军事医学Issue(1)：35-39,5.DOI:10.7644/j.issn.1674-9960.2016.01.009
YAP1在人肺腺癌细胞厄洛替尼耐药中的作用
Effect of YAP1 on erlotinib-resistance in lung adenocarcinoma cells
摘要
Abstract
Objective To explore the effect of Yes-associated protein 1 (YAP1) and potential mechanism on erlotinib ( ER) resistance in lung adenocarcinoma.Methods In PC-9 cells and acquired ER resistant PC-9 ( PC-9/ER) cells, the expression changes in YAP1 gene were measured by quantitative real-time PCR( RT-qPCR) and Western blot.Indirect immunofluorescence was adopted to observe the location of YAP1.PC-9/ER cells were treated with the verteporfin ( VP, YAP1 inhibitor) for 24 h and 48 h, respectively.Expression changes in mRNA and proteins of YAP1, AKT and p-AKT were detected in the presence or absence of VP.The effect of VP was analyzed by drug resistance index using Cell Counting Kit 8(CCK-8) assay.Results The resistance index of PC-9/ER cells was (99.80 ±25.81).Compared with PC-9 cells, the expression levels of YAP1 mRNA and protein were increased in PC-9/ER.The inhibitory efficiency of VP was (50.96 ±5.86)%, and the levels of AKT and p-AKT proteins were down-regulated by the inhibition of YAP1 simultaneously.The half maximal inhibitory concentration (IC50) of PC-9/ER decreased from (11.10 ±2.72) to (1.47 ± 0.32)μmol/L (P =0.024).Resistance index was reduced to one eighth of the original.Conclusion These results indicate that the YAP1 mediates ER resistance in lung adenocarcinoma.Suppression of YAP1 can reduce the resistance through PI3K/AKT signaling pathway.Therefore, YAP1 may be a potential target for lung cancer gene therapy.关键词
YAP1/维替泊芬/肺腺癌/厄洛替尼/耐药/靶向治疗Key words
YAP1/verteporfin/lung adenocarcinoma/erlotinib/drug resistance/target therapy分类
医药卫生引用本文复制引用
王江,王旭东,赵凤仪,韩静,孙华科,孙建国,陈正堂..YAP1在人肺腺癌细胞厄洛替尼耐药中的作用[J].军事医学,2016,(1):35-39,5.基金项目
国家自然科学基金资助项目（81172070，81071786）；重庆市科委重点攻关项目（CSTC 2011AB5032）；第三军医大学青年创新基金资助项目 （）
