PhD Scientific Days 2023
Budapest, 22-23 June 2023
Translational Medicine III.
Enhancement of Modulated Electro-Hyperthermia (mEHT) Effects by Heat Shock Factor 1 (HSF1) Inhibition in Triple Negative Breast Cancer (TNBC) Mouse Model
Előadó neve
Leroy Viana, Pedro Henrique
Neptun code
GKEDSP
Előadó munkahelye
Semmelweis University
Előadó telefonszáma
+36702138189
Előadó e-mail címe
pedro.leroy@phd.semmelweis.hu
Az előadás címe
Enhancement of Modulated Electro-Hyperthermia (mEHT) Effects by Heat Shock Factor 1 (HSF1) Inhibition in Triple Negative Breast Cancer (TNBC) Mouse Model
Szerző(k) neve és munkahelye
Viana, Pedro1; Schvarcz, Csaba1; Danics, Lea1; Besztercei, Balázs1; Aloss, Kenan1; Bokhari, Zahra1; Giunashvili, Nino1; Koós, Zoltán1; Bócsi, Dániel1; Benyó, Zoltán1; Hamar, Péter1
1 Department of Translational Medicine – Semmelweis University
Bemutatás módja
Szóbeli
Szekció
Translational Medicine III.
Language of the presentation
English
Preferred session
Theoretical and Translational Medicine
Összefoglaló szövege
Introduction: Female breast cancer is the most diagnosed cancer worldwide. Triple negative breast cancer (TNBC) is the most aggressive type and is not sensitive to endocrine therapy. Modulated electro-hyperthermia (mEHT) is a non-invasive complementary tumor therapy using an electromagnetic field generated by amplitude modulated 13.56 MHz frequency that induces tumor cell destruction. However, we have demonstrated a strong induction of the heat shock response (HSR) by mEHT, which can result in thermotolerance.
Aim: We hypothesized that downregulation of HSF1 gene sensitizes the transfected tumor cells to mEHT and reduce tumor growth.
Method: A Balb/C isogenic murine TNBC cell line (4T1) was used. HSF1 CRISPR/Cas9 lentiviral knockdown or wild type 4T1 cells were inoculated into mammary gland’s fat pad. Further, wild type tumors were treated with the HSF-1 inhibitor KRIBB11, for 8 days. Four mEHT treatments were performed every two days and the tumor growth was followed by ultrasound and caliper.
Results: Tumor destruction histology and molecular expression changes were assessed. Reduction of tumor size and weight, and enlargement of tumor destruction area were observed in HSF1-KO mEHT-treated mice vs HSF1-KO Sham (HSF1-KO: 43.66 mg ± 20.09 mg; 84.45% ± 15.66% vs Sham: 110.0 mg ± 44.54 mg; 32.1% ± 14.52%, respectively) and Empty Vector mEHT-treated (89.49 mg ± 24.8 mg; 77.24% ± 7.34%, respectively). HSF1 mRNA level was significantly reduced in the KO group (Sham: 0.006180 ± 0.0006644; mEHT-treated: 0.005832 ± 0.001073) when compared to Empty Vector group (Sham: 0.01330 ± 0.002487; mEHT-treated: 0.01732 ± 0.004167). CRISPR/Cas9 lentiviral construct was able to diminish the induction of HSP70 mRNA expression (mEHT-treated: 0.01046 ± 0.005662) when compared to Empty Vector mEHT-treated group (0.02273 ± 0.01385). Immunohistochemistry confirmed the molecular data. Combined therapy of mEHT and KRIBB11 significantly reduced tumor weight (160.3 mg ± 33.26 mg) further compared to monotherapy (mEHT: 236.8 mg ± 46.42 mg; KRIBB11: 312.3 mg ± 41.45 mg).
Conclusion: Therefore, combined mEHT-therapy with HSF1 inhibition can be a possible new strategy of treating TNBC with a great translational potential.
Funding: Tempus Foundation – Stipendium Hungaricum scholarship; SE250+ EFOP-3.6.3-VEKOP-16-2017-00009; TÉT Brazil: 2021-1.2.4-TÉT-2021-00060; Ministry for Innovation and Technology and Hungarian National Research, Development and Innovation Office (ÚNKP-22-4-I-SE-15)
University and Doctoral School
Semmelweis University, Doctoral School of Theoretical and Translational Medicine
Supervisor
Prof. Dr. Hamar Péter
Publication of my abstract
I give consent to the publication of my abstract on the website of the congress.
Kind
Szabad
Status
elfogadva
Accepted presentation method
szóbeli
Előadás fájl jóváhagyás
nem rendelkezett róla
Előadó
6868
Start
14:30
End
14:45
Authors (legacy)
Viana, Pedro1; Schvarcz, Csaba1; Danics, Lea1; Besztercei, Balázs1; Aloss, Kenan1; Bokhari, Zahra1; Giunashvili, Nino1; Koós, Zoltán1; Bócsi, Dániel1; Benyó, Zoltán1; Hamar, Péter1
1 Department of Translational Medicine – Semmelweis University