Department of Respiratory and Critical Care Medicine, Tianjin Medical University General Hospital, 154 Anshan Road, Heping District, Tianjin, China.
Department of Respiratory, Binzhou Central Hospital, Binzhou, China.
Naunyn Schmiedebergs Arch Pharmacol. 2023 Oct;396(10):2417-2426. doi: 10.1007/s00210-023-02460-2. Epub 2023 Apr 4.
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.
肺癌仍然是世界上最常见的癌症，尤其是肺腺癌（LUAD）。尽管经过多年的努力，包括免疫治疗和靶向治疗的应用，LUAD 的生存率并没有显著提高。探索有效的靶点和联合药物对于 LUAD 的治疗至关重要。我们基于癌症基因组图谱（TCGA）数据库对 LUAD 和正常肺组织之间的差异表达基因进行了表征，并确定了 polo 样激酶 1（PLK1）作为枢纽基因。通过使用中药系统药理学数据库和分析平台（TCMSP）进行分析，我们获得了一种与 PLK1 抑制剂结合的中药，并用 Western blot 和 TdT-UTP 缺口末端标记（TUNEL）测定法证实了其生物学功能。在对蛋白表达与临床特征进行综合分析后，GNPNAT1、CCT6A、SMOX、UCK2、PLK1、HMMR 和 ANLN 的表达与年龄、性别和分期显著相关。其中，PLK1 高表达的患者生存率低于 PLK1 低表达的患者，这表明 PLK1 是 LUAD 有前途的治疗靶点。分期和 PLK1 表达可作为 LUAD 的独立预后因素。通过 TCMSP 分析，梓醇与 PLK1 的相关性最强。梓醇与 PLK1 抑制剂协同抑制自噬和铁死亡，但促进 A549 细胞中 caspase-3 介导的细胞凋亡。我们的研究结果强调了 PLK1 抑制剂和梓醇联合治疗 LUAD 患者的潜在药物靶点和联合治疗策略。
