Lovastatin inhibits adipocyte-associated increased proliferation, EMT and aggressiveness of breast cancer cells.

Breast cancer is a significant health concern globally, with obesity exacerbating its prognosis. Despite advancements in therapies, challenges like chemoresistance and metastasis persist, especially in obese patients. Adipokines, upregulated in obese individuals, contribute to breast cancer progression by disrupting multiple signalling pathways. Lovastatin has shown potential as an adjuvant therapy due to its anti-tumour properties. In this study, we aimed to uncover the role of lovastatin in obesity-associated breast cancer. MCF-7 and MDA-MB-231 breast cancer cell lines, along with pre-adipocyte 3T3-L1 cells, were cultured and differentiated into mature adipocytes. Adipocyte-conditioned medium (ACM) was generated and used to culture the breast cancer cells. The effects of lovastatin combined with paclitaxel on cell viability, migration, and cell cycle were evaluated using MTT assay, scratch wound healing assay, and flow cytometry, respectively. Reverse docking was employed to identify potential lovastatin targets. Differentiated 3T3-L1 adipocytes successfully produced ACM, which significantly stimulated proliferation in both MCF-7 and MDA-MB-231 cells. Lovastatin, combined with paclitaxel, notably inhibited cell proliferation and migration, and induced cell cycle arrest in the S phase. Reverse docking identified key pathways and targets affected by lovastatin, including PPAR signalling. The study demonstrated that ACM from differentiated adipocytes enhances breast cancer cell proliferation and migration. Lovastatin effectively inhibits tumourigenic effect of ACM, suggesting its potential as a therapeutic agent for obesity-associated breast cancer via PPAR signalling. Further studies are warranted to validate these results and explore clinical applications.