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04/21/2021 - 06:44 | Wissenschaft

Modulierte Elektrohyperthermie induziert eine ausgeprägte lokale Stressreaktion und Wachstumshemmung bei Maus-Brustkrebs-Isotransplantaten

scientific research
scientific research

Autoren: Csaba András Schvarcz, Lea Danics, Tibor Krenács, Pedro Viana, Rita Béres, Tamás Vancsik, Ákos Nagy, Attila Gyenesei, József Kun, Marko Fonović, Robert Vidmar, Zoltán Benyó, Tamás Kaucsár and Péter Hama,

Abstract: Modulated electrohyperthermia (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, therapyresistant 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 stressrelated Hsp70 and cleaved caspase3 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 mostu upregulated treatmentrelated genes/proteins as revealed by nextgeneration 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 heatshock factor inhibitor KRIBB11 reduced mEHTinduced 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.