Metformin induces mitochondria-mediated and endoplasmic reticulum stress-mediated apoptosis and inhibits angiogenesis-related gene expression in breast cancer cells via targeting VEGF-A/VEGFR2/NRP1.

IF 1.5 4区医学 Q2 MEDICINE, GENERAL & INTERNAL

Croatian Medical Journal Pub Date : 2025-05-07

Ares Alizade, Gulsah Evyapan, Ibrahim Seyfettin Celik, Berna Ozdem

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引用次数: 0

Abstract

Aim: To investigate the apoptotic and anti-angiogenic effects of metformin in human MCF7 breast cancer cells.

Methods: 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.

Results: 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.

Conclusions: 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.

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二甲双胍通过靶向VEGF-A/VEGFR2/NRP1诱导线粒体介导和内质网应激介导的细胞凋亡，抑制乳腺癌细胞血管生成相关基因表达。

目的：探讨二甲双胍对人MCF7乳腺癌细胞的凋亡和抗血管生成作用。方法：采用MTS法和结晶紫法观察二甲双胍对细胞活力的影响，采用创面愈合法观察二甲双胍对细胞迁移的影响。实时聚合酶链反应、Western blot和流式细胞术检测血管生成和凋亡相关基因的表达和蛋白水平。结果：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（10 μM）在治疗48小时后增加了caspase-3、Bax、AIF、CHOP和GRP78的凋亡相关基因和蛋白表达。Bcl-2、Wee1基因及蛋白表达明显降低，血管生成相关基因VEGFA、VEGFR2、NRP1表达明显抑制。结论：我们的研究结果表明，二甲双胍治疗激活细胞凋亡途径，并使血管生成途径失活。虽然这项研究是在体外进行的，没有直接评估血管形成，但观察到血管生成相关基因的下调，表明二甲双胍在基因表达水平上具有潜在的抗血管生成活性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Croatian Medical Journal 医学-医学：内科

CiteScore

3.00

自引率

5.30%

发文量

105

审稿时长

6-12 weeks

期刊介绍： Croatian Medical Journal (CMJ) is an international peer reviewed journal open to scientists from all fields of biomedicine and health related research. Although CMJ welcomes all contributions that increase and expand on medical knowledge, the two areas are of the special interest: topics globally relevant for biomedicine and health and medicine in developing and emerging countries.