Rosuvastatin Ameliorates the Initiation and Progression of Lung Adenocarcinoma via Facilitating PLK1 Inhibition

Background: Lung cancer remains a major global public health challenge, with lung adenocarcinoma being the most prevalent histologic subtype. Rosuvastatin, a widely used lipid-lowering agent, has recently attracted attention for its potential antitumor properties. This study investigates the underlying mechanisms and therapeutic potential of rosuvastatin in lung cancer. Methods: The effects of rosuvastatin were evaluated in lung adenocarcinoma cell lines using Cell Counting Kit-8 (CCK-8), 5-ethynyl-2′-deoxyuridine (EdU) incorporation, Transwell migration and invasion assays, wound-healing assays, and flow cytometry for apoptosis analysis. RNA sequencing identified cell-cycle signaling pathways as the primary targets of rosuvastatin. Analysis of survival curves and differential gene expression between tumor and adjacent non-tumor tissues using public databases, including the Human Protein Atlas, Gene Expression Profiling Interactive Analysis (GEPIA), and Tumor Immune Estimation Resource (TIMER), suggested that polo-like kinase 1 (PLK1) may be a key target mediating the antitumor effects of rosuvastatin. Western blotting and quantitative reverse transcription polymerase chain reaction (qRT-PCR) were used to confirm the differential expression of PLK1 and related cell-cycle proteins in lung adenocarcinoma cells following treatment with different doses of rosuvastatin. Furthermore, rescue experiments with PLK1 knockdown were performed to verify its role in the mechanism of rosuvastatin. A subcutaneous mouse xenograft model was established in vivo to assess the antitumor activity of rosuvastatin via PLK1 inhibition. Results: Rosuvastatin exerted significant antitumor effects against lung adenocarcinoma both in vitro and in vivo. Mechanistic studies indicated that its anticancer activity is mainly mediated by downregulating PLK1 expression. Conclusions: By suppressing PLK1 expression, rosuvastatin inhibited cancer cell proliferation, migration, and invasion. These findings support the potential of rosuvastatin as a therapeutic agent for lung cancer, although further studies are needed to confirm its clinical utility.