Lea Danics1, Csaba Schvarcz1, Zita Zolcsák1, Zoltán Benyó1, Tamás Kaucsár1, Péter Hamar1
1 Institute of Clinical Experimental Research, Semmelweis University, Budapest
Introduction: The effective therapy of triple-negative breast cancer (TNBC) has not yet been achieved. Modulated electro-hyperthermia (mEHT) is a novel antitumor therapy, based on the selective heating of the tumor tissue by a 13.56 MHz radiofrequency current induced electric field.
Aims: Our aim was to investigate the effects of repeated mEHT treatment in triple-negative mammary carcinoma bearing mouse model.
Method: 4T07 cells were inoculated orthotopically in female BALB/c mice. Tumor growth was monitored by digital caliper and ultrasound (Phillips Sonos 5500). The mEHT (n=8) or sham (n=9) treatments started 7 days after inoculation and were repeated 5 times, every other day. Mice were euthanized 1 day after the fifth treatment, tumors were dissected, weighed and processed for histology and molecular biology techniques. The ratio of damaged area compared to the whole tumor area (Tissue Destruction Ratio, TDR) was evaluated on H&E and cleaved caspase-3 stained sections. HSP70, a damage-associated molecular signal, Ki67, a proliferation marker and p21, a tumor suppressor protein expression were analyzed on immunohistochemical staining with the CaseViewer Software (3DHistech).
Results: There was a significant decrease in tumor growth (sham: 5.7x, mEHT: 2.4x relative to pre-treatment (day 6) size, p<0.0001) and weight (sham: 288.3±58.1 mg vs mEHT: 85.3±21.3 mg, p<0.05) in the mEHT treated group, compared to the sham group. The elevation of the HSP70 was 5.2x higher in the treated group (p<0.05). The Ki67+ nucleus/mm2 count was significantly lower (sham: 2823.4±211.9 pcs/mm2 vs mEHT: 1736.7±315.3 pcs/mm2, p<0.05) and the p21+ nucleus/mm2 count showed increasing tendency (sham: 127.0±25.3 pcs/mm2 vs mEHT: 242.2±78.2 pcs/mm2, p = 0,073) in the treated group, compared to the sham group.
Conclusion: Our findings suggest, that repeated mEHT could lower tumor cell proliferation by promoting cell cycle arrest in vivo. Thus, mEHT could be a possible alternative therapeutic strategy for TNBC cancer patients.
Doctoral School: Basic and Translational Medicine
Program: 02. The Mechanisms of Normal and Pathologic Functions of the Circulatory System
Supervisor: Péter Hamar
E-mail address: email@example.com