Aspirin-targeted PD-L1 in lung cancer growth inhibition.

Abstract

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 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.

CONCLUSIONS:

Aspirin suppressed the growth of lung cancer cells via targeting the TAZ/PD-L1 axis.

• Authors: Yixiang Zhang, Changsheng Lv, Yan Dong, Qingkai Yang
• Journal: Thoracic cancer (Thorac Cancer) Vol. 11 Issue 6 Pg. 1587-1593 (06 2020) ISSN: 1759-7714 [Electronic] Singapore
• PMID: 32297484 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2020 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.

Chemical References

• Anti-Inflammatory Agents, Non-Steroidal
• B7-H1 Antigen
• CD274 protein, human
• Aspirin

Topics

• Anti-Inflammatory Agents, Non-Steroidal (pharmacology)
• Aspirin (pharmacology)
• B7-H1 Antigen (antagonists & inhibitors)
• Cell Proliferation
• Gene Expression Regulation, Neoplastic (drug effects)
• Humans
• Lung Neoplasms (drug therapy, immunology, metabolism, pathology)
• Tumor Cells, Cultured