PD-L1失调介导了埃克替尼对EGFR突变晚期非小细胞肺癌的影响

Effect of PD-L1 Dysregulation on Treatment of EGFR Mutant Non-Small Cell Lung Cancer with Icotinib

目的利用表皮生长因子受体(epidermal growth factor receptor,EGFR)突变非小细胞肺癌(non-small cell lung cancer,NSCLC)细胞探究程序性细胞死亡配体1(programmed cell death ligand 1,PDL1)在埃克替尼抗性中的潜在作用。方法采用实时荧光定量PCR(qRT-PCR)和Western印迹检测A549、HCC827和PC-9细胞中p-EGFR和PD-L1的表达水平。MTT方法评估HCC827和PC-9细胞对埃克替尼的敏感性。采用PD-L1敲除来评估对埃克替尼敏感性的影响,并使用小鼠异形移植模型进行体内实验。结果与A549细胞比较,HCC827和PC-9细胞中p-EGFR和PD-L1水平较高。埃克替尼对HCC827和PC-9细胞增殖有显著的抑制作用,并激活细胞凋亡。敲除PD-L1显著降低了埃克替尼对HCC827和PC-9细胞的抑制作用。与sh-NC+埃克替尼组比较,PD-L1敲除在体内降低对埃克替尼的敏感性。结论埃克替尼对EGFR突变NSCLC细胞有抑制作用,PD-L1有助于EGFR突变NSCLC细胞对埃克替尼的敏感性。

Objective To explore the potential role of programmed cell death ligand 1(PDL1)in icotinib resistance by using epidermal growth factor receptor(EGFR)-mutant non-small cell lung cancer(NSCLC)cells.Methods The expression levels of p-EGFR and PD-L1 in A549,HCC827 and PC-9 cells were detected by real-time fluorescent quantitative PCR(qRT-PCR)and Western blotting.MTT method was used to evaluate the sensitivity of HCC827 and PC-9 cells to icotinib.PD-L1 knockout cells were used to evaluate the effect of PD-L1 on the sensitivity of EGFR-mutant NSCLC cells to icotinib,and the patient-derived tumor xenografts mouse model was used for the in vivo experiments.Results Compared with the A549 cells,the expression levels of p-EGFR and PD-L1 were higher in the HCC827 and PC-9 cells.Icotinib significantly inhibited the proliferation and enhanced the apoptosis of HCC827 and PC-9 cells.Knockout of PD-L1 significantly reduced the inhibition of icotinib on HCC827 and PC-9 cells.Compared with the sh-NC+icotinib group,PD-L1 knockout reduced the sensitivity of EGFR-mutant NSCLC cells to icotinib in vivo.Conclusion Icotinib could inhibit EGFR-mutant NSCLC cells,and PD-L1 contribute to the icotinib sensitivity in EGFR-mutant NSCLC cells.