| Autor: |
Schvarcz CA; Institute of Translational Medicine, Semmelweis University, 1094 Budapest, Hungary., Danics L; Institute of Translational Medicine, Semmelweis University, 1094 Budapest, Hungary., Krenács T; 1st Department of Pathology and Experimental Cancer Research, Semmelweis University, 1085 Budapest, Hungary., Viana P; Institute of Translational Medicine, Semmelweis University, 1094 Budapest, Hungary., Béres R; Institute of Translational Medicine, Semmelweis University, 1094 Budapest, Hungary., Vancsik T; Institute of Translational Medicine, Semmelweis University, 1094 Budapest, Hungary., Nagy Á; Molecular Oncohematology Research Group, 1st Department of Pathology and Experimental Cancer Research, Semmelweis University, 1085 Budapest, Hungary., Gyenesei A; Bioinformatics Research Group, Genomics and Bioinformatics Core Facility, János Szentágothai Research Centre, University of Pécs, H-7624 Pécs, Hungary., Kun J; Bioinformatics Research Group, Genomics and Bioinformatics Core Facility, János Szentágothai Research Centre, University of Pécs, H-7624 Pécs, Hungary.; Department of Pharmacology and Pharmacotherapy, Medical School & Szentágothai Research Centre, Molecular Pharmacology Research Group, Centre for Neuroscience, University of Pécs, H-7624 Pécs, Hungary., Fonović M; Department of Biochemistry and Molecular and Structural Biology, Jožef Stefan Institute, 1000 Ljubljana, Slovenia., Vidmar R; Department of Biochemistry and Molecular and Structural Biology, Jožef Stefan Institute, 1000 Ljubljana, Slovenia., Benyó Z; Institute of Translational Medicine, Semmelweis University, 1094 Budapest, Hungary., Kaucsár T; Institute of Translational Medicine, Semmelweis University, 1094 Budapest, Hungary., Hamar P; Institute of Translational Medicine, Semmelweis University, 1094 Budapest, Hungary. |
| Abstrakt: |
Modulated electro-hyperthermia (mEHT) is a selective cancer treatment used in human oncology complementing other therapies. During mEHT, a focused electromagnetic field (EMF) is generated within the tumor inducing cell death by thermal and nonthermal effects. Here we investigated molecular changes elicited by mEHT using multiplex methods in an aggressive, therapy-resistant triple negative breast cancer (TNBC) model. 4T1/4T07 isografts inoculated orthotopically into female BALB/c mice were treated with mEHT three to five times. mEHT induced the upregulation of the stress-related Hsp70 and cleaved caspase-3 proteins, resulting in effective inhibition of tumor growth and proliferation. Several acute stress response proteins, including protease inhibitors, coagulation and heat shock factors, and complement family members, were among the most upregulated treatment-related genes/proteins as revealed by next-generation sequencing (NGS), Nanostring and mass spectrometry (MS). pathway analysis demonstrated that several of these proteins belong to the response to stimulus pathway. Cell culture treatments confirmed that the source of these proteins was the tumor cells. The heat-shock factor inhibitor KRIBB11 reduced mEHT-induced complement factor 4 (C4) mRNA increase. In conclusion, mEHT monotherapy induced tumor growth inhibition and a complex stress response. Inhibition of this stress response is likely to enhance the effectiveness of mEHT and other cancer treatments. |
