Onvansertib inhibits the proliferation and improves the cisplatin-resistance of lung adenocarcinoma via β-catenin/c-Myc signaling pathway.

Polo-like kinase 1 (PLK1) is a key regulator of cell division, and its abnormal expression is related to the progression and prognosis of cancers. However, the effect of PLK1 inhibitor onvansertib on the growth of lung adenocarcinoma (LUAD) has not been explored. In this study, we performed a series of bioinformatics and experimental analyses to comprehensively investigate the role of PLK1 in LUAD. We used CCK-8 assay and colony formation assay to evaluate the growth inhibitory ability of onvansertib. Furthermore, flow cytometry was applied to exploit the effects of onvansertib on cell cycle, apoptosis, and mitochondrial membrane potential. Moreover, the therapeutic potential of onvansertib was assessed in vivo by using xenograft tumor and patient-derived xenograft (PDX) models. We found that onvansertib significantly induced the apoptosis and inhibited the proliferation and migration of LUAD cells. Mechanistically, onvansertib arrested the cells at G2/M phase and enhanced the levels of reactive oxidative species in LUAD. Accordingly, onvansertib regulated the expression of glycolysis-related genes and improved the cisplatin resistance in LUAD. Notably, the protein levels of β-catenin and c-Myc were affected by onvansertib. Taken together, our findings provide insight into the function of onvansertib and shed light on the potential clinical application of onvansertib for the treatment of patients with LUAD.