Effect of YAP1 on erlotinib-resistance in lung adenocarcinoma cells
10.7644/j.issn.1674-9960.2016.01.009
- VernacularTitle:YAP1在人肺腺癌细胞厄洛替尼耐药中的作用
- Author:
Jiang WANG
;
Xudong WANG
;
Fengyi ZHAO
;
Jing HAN
;
Huake SUN
;
Jianguo SUN
;
Zhengtang CHEN
- Publication Type:Journal Article
- Keywords:
YAP1;
verteporfin;
lung adenocarcinoma;
erlotinib;
drug resistance;
target therapy
- From:
Military Medical Sciences
2016;(1):35-39
- CountryChina
- Language:Chinese
-
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.
