Abstract P3-11-17: Statins suppress the aggressive phenotype of triple negative breast cancer cells via modulation of EGFR signalling

Introduction: Triple negative breast cancer (TNBC) accounts for around 15-20% of primary breast cancers and, despite an initially favourable response to chemotherapy, is associated with higher rates of distant metastasis and a particularly poor outcome versus patients whose tumours are hormone receptor-positive. Despite intensive research efforts TNBC still lacks an effective biological target and there is an urgent need for more effective approaches to treat this disease. The use of statins is well documented for the treatment of hypercholesterolemiaand lowering cardiovascular disease risk through their ability to inhibit the HMG CoA reductase enzyme within the mevalonate pathway. Growing evidence also suggests that statins may also lower the risk of developing some forms of cancer including breast cancer and that these agents can improve response to targeted therapy in certain contexts. Studies have suggested that anticancer effects of statins may be mediated though modulation of receptor tyrosine kinase pathways, effects that may be independent of cellular cholesterol levels. In this study we sought to determine the effects of statins on TNBC cell lines in vitro and identify the underlying mechanism of anti-cancer action focusing on RTK pathway modulation. Methods: The effects of statins (Simvastatin, Rosuvastatin and Atorvastatin) were investigated on TNBC (MDA-MB-231) and ER+, luminal A (MCF7) breast cancer models. Cell proliferation was measured via a Ki67 assay and WST assays. Cell wounding assays were used to determine changes in cell migration whilst cytoskeleton changes were examined via immunofluorescence staining for actin (phalloidin) and focal adhesions (vinculin). Western blot analysis was used to investigate signalling pathway changes in response to statin treatment. Results: Statin treatment resulted in loss of MDAMB231 viability and suppression of proliferative capacity in contrast to MCF7 cells which were insensitive to these agents [IC50 (growth) ±SD were [simvastatin: 1.36±0.12μM (MDA231) versus 23.91±0.34μM (MCF7), p 100μM (MCF7)]; [atorvastatin: 5.36±0.12μM (MDA231) versus u003e20μM (MCF7)]. Statin treatment suppressed the endogenous and EGF-stimulated migratory phenotype of MDA231 cells in a dose-dependent manner (mean per-cent reduction in migratory activity for MDA231 cells following simvastatin treatment (5μM) was 56%±6, p Citation Format: Chris Smith, Shafila Alim, Aliki Kadi, Ruba Al Lawati, Madeline Miles, Steve Hiscox. Statins suppress the aggressive phenotype of triple negative breast cancer cells via modulation of EGFR signalling [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P3-11-17.