PhD Scientific Days 2020

Theoretical and Translational V. Lectures

Modulated Electro-hyperthermia Suppresses H19, a Tumor Promoting Long Non-coding RNA, in a Triple Negative Breast Cancer Model

Előadó neve

Dr. Danics, Lea

Előadó munkahelye

Semmelweis University, Institute of Translational Medicine

Előadó telefonszáma

+36206701162

Előadó e-mail címe

danics.lea@med.semmelweis-univ.hu

Az előadás címe

Modulated Electro-hyperthermia Suppresses H19, a Tumor Promoting Long Non-coding RNA, in a Triple Negative Breast Cancer Model

Szerző(k) neve és munkahelye

Lea Danics1, Csaba Schvarcz1, Zita Zolcsák1, Zoltán Benyó1, Tamás Kaucsár1, Péter Hamar1
1 Institute of Translational Medicine, Semmelweis University, Budapest

Szekció

Theoretical and Translational V. Lectures

Language of the presentation

English

Section, first choice

Theoretical and Translational Medicine

Section, second choice

Pathology and Oncology

Összefoglaló szövege

Modulated electro-hyperthermia (mEHT) is a complementary antitumor therapy, based on selective tumor cell killing by a 13.56 MHz radiofrequency induced electric field. H19 long non coding RNA (lncRNA) is involved in tumor progression and metastasis. It’s overexpression is associated with poor prognosis in breast cancer. We observed previously significant tumor inhibitory effects of mEHT.
Our aim was to investigate mEHT related inhibition of H19 lncRNA in triple negative breast cancer (TNBC) spheroids and in TNBC bearing mouse models.
4T1 spheroids were embedded in Matrigel® and treated with mEHT for 30 minutes. Samples were collected 24 hours after treatment and processed for Real-Time PCR (RT-PCR). TNBC cells (4T1, 4T07) were inoculated orthotopically in female BALB/c mice. Tumor growth was monitored in vivo by digital caliper and ultrasound, mice were randomized into groups based on tumor size. Mice were treated with mEHT in monotherapy or in combination with methotrexate (MTX) 2 or 3 times for 30 minutes with 0.7±0.3W power. The tumors were dissected and processed for molecular biologic techniques. H19 expression was measured with RT-PCR, results were normalized to GAPDH.
Single mEHT treatment of 4T1 spheroids reduced significantly H19 expression compared to normothermic control (Ctr:0.004±0.0004, mEHT:0.0006±0.0002, p<0.0001) There was a significant decrease in H19 expression of 4T1 tumors after two (sham:0.068±0.044, mEHT:0.033±0.024, p<0.05) and three mEHT treatments (sham:0.097±0.059 vs mEHT:0.050±0.030, p<0.05) compared to the sham group. In case of combination treatments H19 expression was significantly lower in the mEHT+MTX group compared to MTX only (MTX:0.104±0,038 vs mEHT+MTX:0.056±0.025, p<0.01). The basic expression of H19 was significantly lower in 4T07 tumors compared to the more aggressive 4T1 tumors (4T07:0.006±0.004 vs 4T1:0.399±0.071, p<0.0001). In 4T07 tumors H19 expression didn’t change after 3 mEHT treatments (sham:0.404±0.334 vs mEHT:1.391±1.840, p>0.10) compared to the sham group.
Our results demonstrate, that mEHT can reduce the expression of tumor promoting H19 lncRNA in vitro and in vivo both in monotherapy and in combination with chemotherapy. Our findings suggest, that mEHT as an alternative complementary treatment could promote antitumor therapy by inhibiting the tumor progression mediating H19 lncRNA expression.

Additional Information

Funded by the Hungarian National Research, Development and Innovation Office (NVKP_16-1-2016-0042 Grant) and the grant of Dr. Korányi András az Egészségmegőrzés és Egészségkultúra Fejlesztéséért Alapítvány.

Bemutatás módja

Szóbeli

Kind

Szabad

Status

elfogadva

Accepted presentation method

szóbeli

Előadás fájl jóváhagyás

nem rendelkezett róla

Előadó

2733

Start

16:45

End

17:00

Authors (legacy)

Lea Danics1, Csaba Schvarcz1, Zita Zolcsák1, Zoltán Benyó1, Tamás Kaucsár1, Péter Hamar1
1 Institute of Translational Medicine, Semmelweis University, Budapest