Abstract
Lung cancer is still the most common cancer in the world, especially lung adenocarcinoma (LUAD). Despite years of effort, including the application of immunotherapy and targeted therapy, the survival rate of LUAD has not improved significantly. Exploring effective targets and combination drugs is crucial for the treatment of LUAD. We characterized differentially expressed genes between LUAD and normal lung tissue based on The Cancer Genome Atlas (TCGA) database and identified polo-like kinase 1 (PLK1) as the hub gene. Through an analysis using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), we obtained a combination of Chinese medicine with PLK1 inhibitor, whose biological function we confirmed by western blot and TdT-UTP nick-end labelling (TUNEL) assays. After combined analysis of protein expression with clinical characteristics, GNPNAT1, CCT6A, SMOX, UCK2, PLK1, HMMR and ANLN expression were significantly correlated with age, sex and stage. Among them, the survival rate was lower in patients with high PLK1 expression than in those with low PLK1 expression, making PLK1 a promising therapeutic target for LUAD. Stage and PLK1 expression could be used as independent prognostic factors for LUAD. By TCMSP analysis, tectoridin had the strongest correlation with PLK1. Tectoridin synergized with PLK1 inhibitor to suppress autophagy and ferroptosis but promoted caspase-3-mediated apoptosis in A549 cells. Our findings highlight a potential drug target and the combination therapy strategy of PLK1 inhibitor and tectoridin for LUAD patients.