PhD Scientific Days 2025

Budapest, 7-9 July 2025

Poster Session I. - D: Pathological and Oncological Sciences

Ivermectin Inhibits HSPB1 Phosphorylation and Improves Efficacy of Modulated Electro-hyperthermia in Mouse Breast Cancer Isografts

Name of the presenter

Aloss Kenan

Institute/workplace of the presenter

Department of Pharmacology and Pharmacotherapy-Semmelweis University

Authors

Kenan Aloss1,2, Pedro Henrique Leroy Viana2, Nino Giunashvili2, Syeda Mahak Zahra Bokhari2, Csaba András Schvarcz2, Peter Hamar2

1: Department of Pharmacology and Pharmacotherapy, Semmelweis University
2: Institute of Translational Medicine, Semmelweis University

Text of the abstract

Introduction
Triple-negative breast cancer (TNBC) is the most aggressive breast cancer subtype with limited treatment options. Modulated electro-hyperthermia (mEHT) is a novel adjuvant cancer therapy, that induces selective cancer damage. However, mEHT upregulates heat shock protein beta 1 (HSPB1), a cancer-promoting stress chaperone molecule.
Aim:
we investigated whether ivermectin (IVM), an anthelminthic drug, may synergize with mEHT and enhance its anti-cancer effects by inhibiting HSPB1 phosphorylation.
Methods:
Isogenic 4T1 TNBC cells were inoculated into Balb/C mice and treated with mEHT, IVM, or a combination of both. The tumor size was measured by ultrasound and digital caliper. Protein localization and expression were evaluated by immunohistochemistry and western blot, respectively.
Results:
The mEHT+IVM combination was more effective at inhibiting tumor growth than mEHT or IVM monotherapies. Furthermore, IVM downregulated the phosphorylated form of mEHT-induced HSPB1. Consequently, a combination of mEHT and IVM caused the strongest cancer tissue damage, associated with the strongest pro-apoptotic and anti-proliferative effects. In addition, there was no significant body weight loss in mice treated with mEHT and IVM, indicating that this combination was well-tolerated.
Conclusion:
mEHT combined with IVM is a new, effective, and safe option for the treatment of TNBC.
Funding:
EKÖP-2024-92