Name: Panagiota Megremi
Title: Effect of simvastatin in the presence of hormones on syndecans expression of TNBC cells. An experimental and in silico study.
Date: 5 June 2026
Time: 11:00 am
Zoom link: https://upatras-gr.zoom.us/j/92702932162?pwd=oo2u933CgpbJ8SdUGVXkhyXLuLRGfj.1
Abstract
Triple-negative breast cancer (TNBC) is considered one of the most aggressive and heterogeneous subtypes of breast cancer due to the absence of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2). The limited availability of targeted therapies and the poor prognosis associated with TNBC highlight the need for the identification of novel molecular mechanisms and therapeutic approaches. Syndecans act as co-receptors and, together with extracellular matrix-related receptors, such as CD44 and RHAMM, participate in tumor progression, invasion, metastasis, and cell signaling. In parallel, increasing evidence suggests that statins, particularly lipophilic statins such as simvastatin, exhibit anti-cancer properties through inhibition of the mevalonate pathway and modulation of signaling pathways related to cell proliferation and survival.
In the present study, the effect of simvastatin on the functional properties of highly metastatic triple-negative breast cancer cells, MDA-MB-231 (ERα-/ERβ+) and Hs578T (ERα-/ERβ-), as well as on the expression of specific cellular components related to invasion, metastasis was investigated. The results were correlated with patient databases regarding the expression of these components and their impact on patient survival. Treatment with simvastatin demonstrated a similar cytostatic effect in both cell lines, Hs578T and MDA-MB-231, with IC50 value being 1.018 μΜ and 1.022 μΜ, respectively, suggesting that simvastatin progressively reduces cell viability.
Cell circularity in both cell lines was increased at higher simvastatin concentrations. The sequential increase in simvastatin concentration seemed to progressively alter the morphology, as the cells gradually changed from elongated to circular. At higher simvastatin concentrations, the cells were quite stressed and were found in aggregates, while some of them were dead.
The findings also suggest that simvastatin modulates the expression of extracellular matrix-associated genes in TNBC cells, while hormonal stimulation further influences these effects in a cell type-dependent manner. Alterations in syndecan and CD44 expression patterns indicate a potential involvement of these molecules in the cellular response to simvastatin and hormonal signaling. Moreover, bioinformatics analyses supported the clinical relevance of several studied genes in breast cancer prognosis and progression.
Overall, this study highlights the complex interplay between simvastatin, steroid hormones, and extracellular matrix-associated molecules in TNBC. The results contribute to a better understanding of the molecular mechanisms underlying TNBC progression and support the potential therapeutic value of simvastatin as an adjuvant strategy in aggressive breast cancer subtypes.
Three-member Evaluation Committee
Demitrios Vynios
Professor, Department of Chemistry, Supervisor
Nikos K. Karamanos
Professor, Department of Chemistry
Achilleas D. Theocharis
Professor, Department of Chemistry