High-dose Aspirin-targeted PD-L1 in lung cancer growth inhibition
Background: 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.
Methods: 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.
Results: Following treatment with aspirin, lung cancer cell growth was markedly suppressed. Aspirin (5.0 mM or 4500 mg) 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.