1. Simvastatin is effective in killing the radioresistant breast carcinoma cellsBertram Aschenbrenner, Giulia Negro, Dragana Savic, Maxim Sorokin, Anton A. Buzdin, Ute Maria Ganswindt, Maja Čemažar, Gregor Serša, Sergej Skvortsov, Ira Skvortsova, 2021, original scientific article Abstract: Background. Statins, small molecular 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors, are widely used to lower cholesterol levels in lipid-metabolism disorders. Recent preclinical and clinical studies have shown that statins exert beneficial effects in the management of breast cancer by increasing recurrence free survival. Unfortunately, the underlying mechanisms remain elusive. Materials and methods. Simvastatin, one of the most widely prescribed lipophilic statins was utilized to investigate potential radiosensitizing effects and an impact on cell survival and migration in radioresistant breast cancer cell lines. Results. Compared to parental cell counterparts, radioresistant MDA-MB-231-RR, T47D-RR andAu565-RR cells were characterized by upregulation of 3-hydroxy-3-methylglutharyl-coenzyme A reductase (HMGCR) expression accom-panied by epithelial-to-mesenchymal transition (EMT) activation. Radioresistant breast cancer cells can be killed by simvastatin via mobilizing of a variety of pathways involved in apoptosis and autophagy. In the presence of simvasta-tin migratory abilities and vimentin expression is diminished while E-cadherin expression is increased. Conclusions. The present study suggests that simvastatin may effectively eradicate radioresistant breast carcinoma cells and diminish their mesenchymal phenotypes.
Keywords: radiotherapy, breast cancer, radioresistant cells
Published in DiRROS: 22.07.2024; Views: 143; Downloads: 73
 Full text (1,76 MB)
This document has many files! More... |
2. Molecular heterogeneity in breast carcinoma cells with increased invasive capacitiesGiulia Negro, Bertram Aschenbrenner, Simona Kranjc Brezar, Maja Čemažar, Andrej Cör, Gorana Gašljević, Maxim Sorokin, Anton A. Buzdin, Maurizio Callari, Irma Kvitsaridze, 2020, original scientific article Abstract: Metastatic progression of breast cancer is still a challenge in clinical oncology. Therefore, an elucidation how carcinoma cells belonging to different breast cancer subtypes realize their metastatic capacities is needed. The aim of this study was to elucidate a similarity of activated molecular pathways underlying an enhancement of invasiveness of carcinoma cells belonging to different breast carcinoma subtypes. Materials and methods. In order to reach this aim, parental and invasive (INV) MDA-MB-231 (triple-negative), T47D (hormone receptor-positive), and Au565 (Her2-positive) breast carcinoma cells were used and their molecular phenotypes were compared using a proteomic approach. Results. Independently from breast cancer subtypes, INV cells have demonstrated fibroblast-like morphology accompanied by enhancement of invasive and migratory capacities, increased expression of cancer stem cell markers, and delayed tumor growth in in vivo animal models. However, the global proteomic analysis has highlighted that INV cells were different in protein expressions from the parental cells, and Her2-positive Au565-INV cells showed the most pronounced molecular differences compared to the triple-negative MDA-MB-231-INV and hormone receptor-positive T47D-INV cells. Although Au565-INV breast carcinoma cells possessed the highest number of deregulated proteins, they had the lowest overlapping in proteins commonly expressed in MDA-MB-231-INV and T47D-INV cells. Conclusions. We can conclude that hormone receptor-positive cells with increased invasiveness acquire the molecular characteristics of triple-negative breast cancer cells, whereas Her2-positive INV cells specifically changed their own molecular phenotype with very limited partaking in the involved pathways found in the MDA-MB-231-INV and T47D-INV cells. Since hormone receptor-positive invasive cells share their molecular properties with triple-negative breast cancer cells, we assume that these types of metastatic disease can be treated rather equally with an option to add anti-hormonal agents. In contrast, Her2-positive metastasis should be carefully evaluated for more effective therapeutic approaches which are distinct from the triple-negative and hormone-positive metastatic breast cancers.
Keywords: breast cancer, cancer stem cells, invasiveness, migration, metastasis
Published in DiRROS: 11.07.2024; Views: 136; Downloads: 38
Full text (2,52 MB) |
