Synergistic Effects of Oxaliplatin, 5-Fluorouracil, and Novel Synthetic Uracil Analog U-359 on Breast Cancer Cell Carcinogenesis DOI Open Access
Angelika Długosz-Pokorska, Tomasz Janecki, Anna Janecka

et al.

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(7), P. 2964 - 2964

Published: March 25, 2025

Breast cancer presents significant global challenges, necessitating effective treatments to combat drug resistance and minimize chemotherapy side effects. This study evaluated the cytotoxic effects of U-359, Oxaliplatin (Ox), 5-Fluorouracil (5-FU) in MCF-7 MCF-10A cells using MTT RealTime-GLO assays. Morphological changes were assessed by light microscopy following Wright-Giemsa staining. Apoptosis induction was studied qPCR for apoptotic markers, RealTime-Glo™ Annexin V assay, cleaved PARP1 ELISA assay. Caspase 8 9 activities, ABCB1, ABCG2, NF-κB protein levels quantified ELISA. Synergy analyzed Bliss Independence Model. The results indicated that combining U-359 with Ox 5-FU enhanced cytotoxicity compared individual treatments. induced apoptosis-associated morphological cells, which augmented treatment. assays confirmed up-regulation pro-apoptotic markers down-regulation anti-apoptotic alone or combination. Elevated suggested robust apoptosis 5-FU. activity demonstrated a activation caspase 9, implicating both pathways. Furthermore, down-regulated up-regulated alone. Model revealed strong synergistic interactions (SI < 1) between 5-FU, particularly reducing ABCB1 levels. combined shows potential overcoming breast enhancing modulating resistance. Further clinical studies are needed optimize treatment improve outcomes.

Language: Английский

Synergistic Effects of Oxaliplatin, 5-Fluorouracil, and Novel Synthetic Uracil Analog U-359 on Breast Cancer Cell Carcinogenesis DOI Open Access
Angelika Długosz-Pokorska, Tomasz Janecki, Anna Janecka

et al.

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(7), P. 2964 - 2964

Published: March 25, 2025

Breast cancer presents significant global challenges, necessitating effective treatments to combat drug resistance and minimize chemotherapy side effects. This study evaluated the cytotoxic effects of U-359, Oxaliplatin (Ox), 5-Fluorouracil (5-FU) in MCF-7 MCF-10A cells using MTT RealTime-GLO assays. Morphological changes were assessed by light microscopy following Wright-Giemsa staining. Apoptosis induction was studied qPCR for apoptotic markers, RealTime-Glo™ Annexin V assay, cleaved PARP1 ELISA assay. Caspase 8 9 activities, ABCB1, ABCG2, NF-κB protein levels quantified ELISA. Synergy analyzed Bliss Independence Model. The results indicated that combining U-359 with Ox 5-FU enhanced cytotoxicity compared individual treatments. induced apoptosis-associated morphological cells, which augmented treatment. assays confirmed up-regulation pro-apoptotic markers down-regulation anti-apoptotic alone or combination. Elevated suggested robust apoptosis 5-FU. activity demonstrated a activation caspase 9, implicating both pathways. Furthermore, down-regulated up-regulated alone. Model revealed strong synergistic interactions (SI < 1) between 5-FU, particularly reducing ABCB1 levels. combined shows potential overcoming breast enhancing modulating resistance. Further clinical studies are needed optimize treatment improve outcomes.

Language: Английский

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