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二甲双胍可提高阿霉素在小鼠乳腺癌中的疗效,并增加CD8 + T细胞频率。

Metformin boosts doxorubicin efficacy and increases CD8 + T cell frequency in mouse breast cancer.

作者信息

Hassani Elaheh, Mozzendizaji Sahand, Shafiei-Irannejad Vahid, Mohammadzadeh Adel

机构信息

Student Research Committee, Urmia University of Medical Sciences, Urmia, Iran.

Department of Immunology, Faculty of Medicine, Kurdistan University of Medical Sciences, Sanandaj, Iran.

出版信息

Clin Transl Oncol. 2025 May;27(5):2060-2066. doi: 10.1007/s12094-024-03764-2. Epub 2024 Oct 29.

Abstract

PURPOSE

Breast cancer is a leading cause of cancer-related deaths among women worldwide. The presence and function of CD8 + T cells in the tumor microenvironment have been associated with better patient outcomes. Drug toxicity has posed a significant challenge to the clinical implementation of chemotherapy-based strategies in cancer treatment.

METHODS

In this study, we employed flow cytometry to investigate the potential synergistic immunomodulatory effects on CD8 + T cells in a mouse model of breast cancer by combining metformin, an anti-diabetic medication, with doxorubicin.

RESULTS

Through flow cytometry analysis, we observed that the combination of the two drugs led to an increased percentage of CD8 + T cells compared to either drug alone. The modulation of HIF-1α and  STAT3 gene expression in the combination group further confirmed the efficacy of this approach.

CONCLUSIONS

Our findings suggest that combining metformin with doxorubicin can enhance the anticancer activity of doxorubicin and decrease its cytotoxicity in a 4T1 breast cancer mouse model.

摘要

目的

乳腺癌是全球女性癌症相关死亡的主要原因。肿瘤微环境中CD8 + T细胞的存在和功能与患者更好的预后相关。药物毒性对基于化疗的癌症治疗策略的临床实施构成了重大挑战。

方法

在本研究中,我们通过将抗糖尿病药物二甲双胍与阿霉素联合使用,采用流式细胞术研究其在乳腺癌小鼠模型中对CD8 + T细胞的潜在协同免疫调节作用。

结果

通过流式细胞术分析,我们观察到与单独使用任何一种药物相比,两种药物联合使用导致CD8 + T细胞百分比增加。联合组中HIF-1α和STAT3基因表达的调节进一步证实了该方法的有效性。

结论

我们的研究结果表明,在4T1乳腺癌小鼠模型中,二甲双胍与阿霉素联合使用可增强阿霉素的抗癌活性并降低其细胞毒性。

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