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Background <p>Breast cancer is the most common cancer in women. While treatments exist, combination therapies may enhance effectiveness and reduce drug resistance. Metformin-a common diabetes medication has shown promising anticancer properties. Azacitidine, primarily an epigenetic regulator, also exhibits anticancer effects.</p> Methods and materials <p>The GSE45827 dataset was analyzed for differentially expressed genes (DEGs) using GEO2R and ShinyGO tools. Protein-protein interaction (PPI) networks were constructed with STITCH and Cytoscape, and key genes were identified using MCODE. Gene expression profiles of selected targets were compared between tumor and matched normal tissues using GTEx Portal and TNMPlot databases. Kaplan-Meier plotter was used for survival analysis, and potential drug targets were identified with Way2Drug. In vitro effects of metformin, azacitidine, and their combination on MDA-MB-231 cells were assessed using MTT assay, isobologram analysis, wound-healing assay, and real-time PCR for <i>CCND1</i>, <i>ELAVL1</i>, and <i>EIF4EBP1</i> gene expression. Statistical analysis was performed.</p> Results <p>Bioinformatics analysis identified <i>CCND1</i>, <i>ELAVL1</i>, and <i>EIF4EBP1</i> as key genes in breast cancer pathogenesis. MTT assays showed that both drugs reduced cell viability in a dose-dependent manner. Isobologram analysis confirmed a strong synergistic effect from the combination. Wound-healing assays revealed significant inhibition of cancer cell migration. Real-time qPCR showed gene expression changes consistent with inhibition of cancer progression.</p> Conclusion <p>The metformin-azacitidine combination synergistically suppresses breast cancer cell proliferation, likely through coordinated modulation of <i>CCND1</i>, <i>ELAVL1</i>, and <i>EIF4EBP1</i>. These findings highlight the potential of this novel drug combination in breast cancer treatment.</p>

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Combined anti-tumor effects of metformin and azacitidine in breast cancer cells

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年10月1日

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  • Setayesh Sadat Hosseini,
  • Nahid Askari,
  • Mohammad Mehdi Yaghoobi

摘要

Background

Breast cancer is the most common cancer in women. While treatments exist, combination therapies may enhance effectiveness and reduce drug resistance. Metformin-a common diabetes medication has shown promising anticancer properties. Azacitidine, primarily an epigenetic regulator, also exhibits anticancer effects.

Methods and materials

The GSE45827 dataset was analyzed for differentially expressed genes (DEGs) using GEO2R and ShinyGO tools. Protein-protein interaction (PPI) networks were constructed with STITCH and Cytoscape, and key genes were identified using MCODE. Gene expression profiles of selected targets were compared between tumor and matched normal tissues using GTEx Portal and TNMPlot databases. Kaplan-Meier plotter was used for survival analysis, and potential drug targets were identified with Way2Drug. In vitro effects of metformin, azacitidine, and their combination on MDA-MB-231 cells were assessed using MTT assay, isobologram analysis, wound-healing assay, and real-time PCR for CCND1, ELAVL1, and EIF4EBP1 gene expression. Statistical analysis was performed.

Results

Bioinformatics analysis identified CCND1, ELAVL1, and EIF4EBP1 as key genes in breast cancer pathogenesis. MTT assays showed that both drugs reduced cell viability in a dose-dependent manner. Isobologram analysis confirmed a strong synergistic effect from the combination. Wound-healing assays revealed significant inhibition of cancer cell migration. Real-time qPCR showed gene expression changes consistent with inhibition of cancer progression.

Conclusion

The metformin-azacitidine combination synergistically suppresses breast cancer cell proliferation, likely through coordinated modulation of CCND1, ELAVL1, and EIF4EBP1. These findings highlight the potential of this novel drug combination in breast cancer treatment.