PhD Scientific Days 2024

Poster Session Q - Pathological and Oncological Sciences 2.

Targeting hypoxia in combination with paclitaxel to enhance therapeutic efficacy in triple-negative breast cancer

Előadó neve

Svajda, Laura

Neptun code

I45MI7

Előadó munkahelye

Department of Experimental Pharmacology and the National Tumor Biology Laboratory, National Institute of Oncology, Budapest, Hungary

Előadó telefonszáma

+36307132930

Előadó e-mail címe

laura.svajda96@gmail.com

Az előadás címe

Targeting hypoxia in combination with paclitaxel to enhance therapeutic efficacy in triple-negative breast cancer

Szerző(k) neve és munkahelye

Laura Svajda^1,2, Ivan Ranđelović¹, Sára Eszter Surguta¹, Marcell Baranyi³, Mihály Cserepes^1,2, József Tóvári^1,2

1: Department of Experimental Pharmacology and the National Tumor Biology Laboratory, National Institute of Oncology, Budapest, Hungary
2: Doctoral School of Semmelweis University, Budapest, Hungary
3: Department of Pathology, Forensic and Insurance Medicine, Semmelweis University, Budapest, Hungary

Bemutatás módja

Poszter

Szekció

Poster Session Q - Pathological and Oncological Sciences 2.

Language of the presentation

English

Összefoglaló szövege

Introduction: The inadequate blood supply of solid tumors leads to areas within the tumor lacking oxygen, known as tumor hypoxia. This condition significantly contributes to the advancement of triple-negative breast cancer (TNBC) by enhancing its ability to spread. Therefore, addressing hypoxia becomes crucial in cancer treatment strategies. In our study, we explored the effects of a promising drug, acriflavine, which targets hypoxia-inducible factors (HIF). To enhance its efficacy and overcome the limitations of hypoxia-targeting drugs used alone, we combined acriflavine with paclitaxel, a commonly used chemotherapy agent. Furthermore, we evaluated the combinatory efficacy of an epithelial-mesenchymal transition inhibitory drug, rolipram as well.
Material and methods: The individual effects and the synergy between the two drugs were evaluated on TNBC cell lines using the Sulforhodamine B assay and the Synergy Finder software. To test the in vivo toxicity and effectiveness of acriflavine and the drug combination, NOD SCID mice were orthotopically inoculated with the MDA-MB-231 cell line. We conducted both quantitative and qualitative analyses of various genes associated with tumor progression by measuring mRNA and protein expression levels through qPCR, western blotting, and immunohistochemistry. HIF-1 activation was induced by either incubating cells at 1% oxygen or treating them with CoCl2.
Results: We found that acriflavine effectively inhibited the growth and migration of triple-negative breast cancer cells under hypoxic conditions. The acriflavine and paclitaxel combination showed synergistic effects, suppressing tumor growth and metastasis in breast cancer models. Molecular analysis revealed that the combination therapy downregulated the hypoxia pathway. Furthermore, adding rolipram, a drug inhibiting epithelial-mesenchymal transition, to the combination further reduced the motility of hypoxic triple-negative breast cancer cells.
Conclusion: In summary, our study identified novel drug combinations capable of efficiently combating triple-negative breast cancer by targeting hypoxia signaling and inhibiting cell migration and metastasis formation.
Funding: The research was financially supported by the National Tumor Biology Laboratory under the National Laboratories Program (2022-2.1.1-NL-2022-00010), the Hungarian Thematic Excellence Program (TKP2021-EGA-44) and the National Research, Development and Innovation Office's Hungarian Scientific Research Fund (NKFIH-OTKA) grants K147410 (JT) and PD142272 (MC).
E-mail: svajda.laura@ext.oncol.hu
University: Doctoral School of Semmelweis University, Budapest, Hungary
Supervisors: Dr. József Tóvári and Dr. Cserepes Mihály

University

Semmelweis University

Publication of my abstract

I do not give consent to the publication of my abstract on the website of the congress.

Előadó születési éve

1996

Kind

Szabad

Status

elfogadva

Accepted presentation method

poszter

Előadás fájl jóváhagyás

nem rendelkezett róla

Előadó

8263

Start

16:40

End

16:43