Alizade Ares, Evyapan Gulsah, Celik Ibrahim Seyfettin, Ozdem Berna
Ares Alizade, Department of Medical Pharmacology, Faculty of Medicine Van Yuzuncu Yil University, Van, Turkey,
Croat Med J. 2025 May 7;66(2):115-124. doi: 10.3325/cmj.2025.66.115.
To investigate the apoptotic and anti-angiogenic effects of metformin in human MCF7 breast cancer cells.
The effect of metformin on cell viability was assessed by MTS and crystal violet assays, and its effect on cell migration was evaluated by the wound healing assay. The gene expression and protein levels of angiogenesis- and apoptosis-related genes were determined by real-time polymerase chain reaction, Western blot, and flow cytometry.
Metformin reduced the viability and migration of breast cancer cells compared with the control group. Furthermore, metformin (10 μM) increased the apoptosis-related gene and protein expression of caspase-3, Bax, AIF, CHOP and GRP78 48 hours after treatment compared with the control group. In contrast, it significantly decreased Bcl-2 and Wee1 gene and protein expression and suppressed angiogenesis-related genes VEGFA, VEGFR2, and NRP1.
Our results suggest that metformin treatment activates apoptosis pathways and inactivates the angiogenesis pathway. Although this study was conducted in vitro and did not directly evaluate blood vessel formation, the observed downregulation of angiogenesis-related genes suggests potential anti-angiogenic activity of metformin at the gene expression level.
研究二甲双胍对人MCF7乳腺癌细胞的凋亡及抗血管生成作用。
通过MTS和结晶紫试验评估二甲双胍对细胞活力的影响，通过伤口愈合试验评估其对细胞迁移的影响。采用实时聚合酶链反应、蛋白质免疫印迹法和流式细胞术检测血管生成和凋亡相关基因的基因表达及蛋白质水平。
与对照组相比，二甲双胍降低了乳腺癌细胞的活力和迁移能力。此外，与对照组相比，二甲双胍（10μM）在处理48小时后增加了凋亡相关基因以及半胱天冬酶-3、Bax、凋亡诱导因子、CHOP和葡萄糖调节蛋白78的蛋白质表达。相反，它显著降低了Bcl-2和Wee1基因及蛋白质表达，并抑制了血管生成相关基因VEGFA、VEGFR2和神经纤毛蛋白1。
我们的结果表明，二甲双胍治疗可激活凋亡途径并使血管生成途径失活。尽管本研究是在体外进行的，并未直接评估血管形成，但观察到的血管生成相关基因的下调表明二甲双胍在基因表达水平具有潜在的抗血管生成活性。
