Department of Thoracic Surgery, The First Affiliated Hospital of Dalian Medicine University, Dalian, China.
Department of Oncology, The First Affiliated Hospital of Dalian Medical University, Dalian, China.
Thorac Cancer. 2020 Jun;11(6):1587-1593. doi: 10.1111/1759-7714.13433. Epub 2020 Apr 15.
Aspirin is a classic anti-inflammatory drug and its anticancer effect has been previously explored in many types of cancer including colorectal cancer therapy. Programmed cell death-ligand 1 (PD-L1) is widely expressed in tumor cells and displays an inhibitory role in antitumor immunity. This study aimed to clarify the role of PD-L1 in aspirin-suppressed lung cancer.
The inhibitory effect of aspirin on lung cancer cell proliferation was assessed using an MTT cell viability assay. The role of aspirin in the modulation of PD-L1 expression was analyzed by western blot or RT-PCR assays. In lung cancer cells, the influence of aspirin on PD-L1 promoter activity was detected using a luciferase reporter assay. The interaction of TAZ with PD-L1 promoter in the cells, with or without aspirin administration, was tested via chromatin immunoprecipitation (ChIP) analysis. The function of PD-L1 in aspirin-mediated growth inhibition of lung cancer was examined using a cell viability assay.
Following treatment with aspirin, lung cancer cell growth was markedly suppressed. Aspirin was able to markedly decrease the expression of PD-L1 at the mRNA and protein levels in lung cancer cells. For the mechanism study, we found that the promoter of PD-L1 was inactivated by aspirin via TAZ transcriptional coactivator in the cells. With regard to the functional investigation, aspirin was capable of resisting cell proliferation and PD-L1 overexpression abolished aspirin-depressed cell proliferation in lung cancer.
Aspirin suppressed the growth of lung cancer cells via targeting the TAZ/PD-L1 axis.
阿司匹林是一种经典的抗炎药物，其在多种癌症中的抗癌作用，包括结直肠癌治疗，已被广泛研究。程序性死亡配体 1（PD-L1）广泛表达于肿瘤细胞，并在抗肿瘤免疫中发挥抑制作用。本研究旨在阐明 PD-L1 在阿司匹林抑制肺癌中的作用。
采用 MTT 细胞活力测定法评估阿司匹林对肺癌细胞增殖的抑制作用。通过 Western blot 或 RT-PCR 检测阿司匹林对 PD-L1 表达的调节作用。在肺癌细胞中，通过荧光素酶报告基因检测法检测阿司匹林对 PD-L1 启动子活性的影响。通过染色质免疫沉淀（ChIP）分析检测 TAZ 在有无阿司匹林给药时与 PD-L1 启动子的相互作用。通过细胞活力测定法检测 PD-L1 在阿司匹林介导的肺癌生长抑制中的作用。
阿司匹林处理后，肺癌细胞生长明显受到抑制。阿司匹林能显著降低肺癌细胞中 PD-L1 的 mRNA 和蛋白水平。在机制研究方面，我们发现阿司匹林通过细胞中的 TAZ 转录共激活因子使 PD-L1 启动子失活。关于功能研究，阿司匹林能够抵抗细胞增殖，而 PD-L1 过表达则消除了阿司匹林对肺癌细胞增殖的抑制作用。
阿司匹林通过靶向 TAZ/PD-L1 轴抑制肺癌细胞的生长。
