Drug Des Devel Ther. 2026 Feb 16;20:579427. doi: 10.2147/DDDT.S579427. eCollection 2026.

ABSTRACT

BACKGROUND: Lung cancer is one of the leading causes of cancer-related deaths, among which NSCLC accounts for approximately 80-85% of all lung cancer cases. Paclitaxel (TAX) is a commonly used chemotherapeutic drug, but it is easy to cause drug resistance. Fluvastatin has anti-cancer potential, but the mechanism of its reversal of drug resistance is unclear.

METHODS: The study was divided into four groups: the A549 control group, the A549/Tax control group, the A549 Fluvastatin-treated group, and the A549/Tax Fluvastatin-treated group. CCK-8, Transwell, and flow cytometry assays were used to detect fluvastatin's effects on cell proliferation, migration, invasion, and apoptosis. Transcriptomics, proteomics, and acetylomics were combined to explore the potential molecular mechanisms.

RESULTS: The preliminary results showed that fluvastatin inhibited the proliferation, migration and invasion of A549 and A549/Tax cells and promoted their apoptosis. Multi-omics analysis revealed that a large number of differentially expressed molecules were detected in both the A549-Fluvastatin vs A549-NC group and the A549/Tax-Fluvastatin vs A549/Tax-NC group, and these molecules were significantly enriched in multiple biological processes and signaling pathways. This suggests that fluvastatin may exert its effects through the synergistic regulation of multiple molecules and pathways. Integrated multi-omics analysis identified several key molecules (for example, HMGCR, RDH11, HSPB1) and acetylated protein-target gene pairs (for example, P09874-BCL2, P42224-PTGS2, P04150-CCND3), which may mediate the antitumor mechanism of fluvastatin.

CONCLUSION: This study indicates that fluvastatin has the potential to reverse TAX resistance in lung cancer, and the results of multi-omics analysis provide a theoretical basis for the exploration of potential therapeutic targets in the future.

PMID:41728357 | PMC:PMC12922964 | DOI:10.2147/DDDT.S579427