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.