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(Landmark Ed)"],"abstract":"<jats:p>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\u2032-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.<\/jats:p>","DOI":"10.31083\/fbl49156","type":"journal-article","created":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T09:29:27Z","timestamp":1777454967000},"source":"Crossref","is-referenced-by-count":0,"title":["Rosuvastatin Ameliorates the Initiation and Progression of Lung Adenocarcinoma via Facilitating PLK1 Inhibition"],"prefix":"10.31083","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-2565-0225","authenticated-orcid":true,"given":"Jie","family":"Yin","sequence":"first","affiliation":[{"name":"Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Soochow University, 215006 Suzhou, Jiangsu, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1100-5440","authenticated-orcid":true,"given":"Jianjie","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Soochow University, 215006 Suzhou, Jiangsu, China"},{"name":"Institute of Respiratory Diseases, Soochow University, 215006 Suzhou, Jiangsu, China"},{"name":"Suzhou Key Laboratory for Respiratory Diseases, 215006 Suzhou, Jiangsu, China"},{"name":"Department of Cancer Diagnosis and Treatment Center, Affiliated Hospital of Jiangnan University, 214000 Wuxi, Jiangsu, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5642-8714","authenticated-orcid":true,"given":"Yinhua","family":"Gong","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, The First Affiliated Hospital of Soochow University, 215006 Suzhou, Jiangsu, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-9823-5076","authenticated-orcid":true,"given":"Wenting","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Soochow University, 215006 Suzhou, Jiangsu, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-8605-7160","authenticated-orcid":true,"given":"Xinyu","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Soochow University, 215006 Suzhou, Jiangsu, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-7381-7579","authenticated-orcid":true,"given":"Chang","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Soochow University, 215006 Suzhou, Jiangsu, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7845-5660","authenticated-orcid":true,"given":"Yang","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Soochow University, 215006 Suzhou, Jiangsu, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-1243-8180","authenticated-orcid":true,"given":"Yili","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Soochow University, 215006 Suzhou, Jiangsu, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0472-1003","authenticated-orcid":true,"given":"Jianjun","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Soochow University, 215006 Suzhou, Jiangsu, China"},{"name":"Institute of Respiratory Diseases, Soochow University, 215006 Suzhou, Jiangsu, China"},{"name":"Suzhou Key Laboratory for Respiratory Diseases, 215006 Suzhou, Jiangsu, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4035-3583","authenticated-orcid":true,"given":"Lei","family":"Gu","sequence":"additional","affiliation":[{"name":"Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Soochow University, 215006 Suzhou, Jiangsu, China"},{"name":"Institute of Respiratory Diseases, Soochow University, 215006 Suzhou, Jiangsu, China"},{"name":"Suzhou Key Laboratory for Respiratory Diseases, 215006 Suzhou, Jiangsu, 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