genel tıp derg

Genel Tıp Dergisi

2602-3741

Selcuk University

10.54005/geneltip.1686771

Clinical Oncology Clinical Sciences (Other)

Klinik Onkoloji Klinik Tıp Bilimleri (Diğer)

Empagliflozin Modulates Angiogenesis and Migration Through the NF-κB1 Axis in Breast Cancer Cells

Empagliflozin’in Meme Kanseri Hücrelerinde NF-κB1 Aracılı Anjiyogenez ve Hücre Göçü Üzerine Etkisi

https://orcid.org/0000-0003-2444-4258

Bal Albayrak

Merve Gulsen

KOCAELİ ÜNİVERSİTESİ, TIP FAKÜLTESİ

https://orcid.org/0000-0003-4902-4022

Korak

Tuğcan

KOCAELİ ÜNİVERSİTESİ, TIP FAKÜLTESİ, TIP PR.

https://orcid.org/0000-0002-6438-7385

Yanar

Sevinc

SAKARYA ÜNİVERSİTESİ, TIP FAKÜLTESİ, TIP PR.

https://orcid.org/0009-0005-1628-5367

Kayır

Nihal

ANKARA MEDİPOL ÜNİVERSİTESİ, TIP FAKÜLTESİ, TIP PR. (ÜCRETLİ)

https://orcid.org/0000-0002-9675-3714

Akpınar

Gürler

KOCAELİ ÜNİVERSİTESİ, TIP FAKÜLTESİ, TIP PR.

https://orcid.org/0000-0001-8527-2096

Kasap

Murat

KOCAELİ ÜNİVERSİTESİ, TIP FAKÜLTESİ, TIP PR.

08 29 2025

35 4 696 703 04 29 2025 06 10 2025

1990

Genel Tıp Dergisi

AbstractBackground/Aims:Triple-negative breast cancer (TNBC) and hormone receptor-positive breast cancer remain challenging to treat due to their aggressive behavior and resistance to conventional therapies. Empagliflozin (EMPA), a sodium-glucose co-transporter 2 (SGLT2) inhibitor, has recently attracted attention for its potential anticancer properties. This study aimed to evaluate the effects of EMPA on cell viability, migration, and gene expression in breast cancer cell lines, focusing on its role in modulating angiogenesis and epithelial-to-mesenchymal transition (EMT) pathways.Methods:The effects of EMPA were assessed in MDA-MB-231 (TNBC) and MCF-7 (Luminal A) breast cancer cell lines using WST-1 cytotoxicity assays, scratch wound migration assays, and quantitative reverse transcription PCR (qRT-PCR). Gene expression analyses were conducted for NF-κB, N-cadherin, VEGFA, and FGF1 to investigate EMPA’s impact on inflammation, angiogenesis, and EMT.Results:EMPA exhibited dose-dependent cytotoxicity, with MCF-7 cells showing greater sensitivity (IC₅₀: 521 µM) compared to MDA-MB-231 cells (IC₅₀: 1080 µM). EMPA significantly inhibited cell migration in both cell lines. In MDA-MB-231 cells, qRT-PCR revealed downregulation of NF-κB, VEGFA, and FGF1, indicating anti-inflammatory and anti-angiogenic activity. In contrast, MCF-7 cells showed NF-κB upregulation along with VEGFA and FGF1 downregulation, suggesting a subtype-specific molecular response.Conclusions:EMPA suppresses breast cancer cell proliferation, migration, and angiogenic signaling, potentially through NF-κB modulation. Its distinct effects on different breast cancer subtypes suggest a context-dependent therapeutic potential. These findings support further investigation into EMPA as a repurposed agent for targeted breast cancer therapy, particularly in aggressive forms such as TNBC.

Giriş/Amaç:Üçlü negatif meme kanseri (TNBC) ve hormon reseptörü pozitif meme kanseri, agresif seyirleri ve geleneksel tedavilere karşı dirençleri nedeniyle tedavisi zor olan alt tiplerdir. Sodyum-glukoz ko-transporter 2 (SGLT2) inhibitörü olan empagliflozin (EMPA), son dönemde potansiyel antikanser özellikleri ile dikkat çekmektedir. Bu çalışmanın amacı, EMPA’nın meme kanseri hücre hatları üzerindeki hücre canlılığı, göçü ve gen ekspresyonu üzerindeki etkilerini değerlendirmek ve özellikle anjiyogenez ile epitel-mezenkimal geçiş (EMT) yollarındaki düzenleyici rolünü incelemektir.Yöntemler:EMPA’nın etkileri, MDA-MB-231 (TNBC) ve MCF-7 (Luminal A) hücre hatlarında WST-1 sitotoksisite testi, yara iyileşme (scratch) testi ve qRT-PCR ile değerlendirilmiştir. NF-κB, N-kaderin, VEGFA ve FGF1 genlerinin ekspresyon düzeyleri analiz edilmiştir.Bulgular:EMPA, her iki hücre hattında da doz bağımlı sitotoksisite ve göç inhibisyonu göstermiştir. MCF-7 hücreleri EMPA’ya daha duyarlı bulunmuştur (IC₅₀: 521 µM). MDA-MB-231 hücrelerinde NF-κB, VEGFA ve FGF1 baskılanırken, MCF-7 hücrelerinde NF-κB artışı ile birlikte VEGFA ve FGF1 azalması gözlemlenmiştir.Sonuç:EMPA, meme kanseri hücrelerinde proliferasyon, göç ve anjiyogenez süreçlerini baskılayarak antikanser etki göstermektedir. Alt tiplere özgü moleküler yanıtları nedeniyle, özellikle TNBC gibi agresif alt tiplerde yeni tedavi stratejileri için umut vadetmektedir.

Empagliflozin Breast Cancer NF-κB Signaling Angiogenesis Cell Migration

Empagliflozin Meme Kanseri NF-κB Sinyal Yolağı Anjiyogenez Hücre Göçü

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