Oral Combined Probiotics Clostridium butyricum and Akkermansia muciniphila Inhibits the Progression of 4T1 Breast Cancer by Activating Bcl-2/Bax Pathway

IF 2.9 2区医学 Q2 ONCOLOGY

Cancer Medicine Pub Date : 2025-06-11 DOI:10.1002/cam4.70987

Xiaowei Li, Dengxiong Hua, Daoyan Wu, Wei Hong, Yingqian Kang, Lei Tang, Qin Yang, Xinxin Wang, Boyan Li, Renmin Li, Zhenghong Chen, Guzhen Cui

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引用次数: 0

Abstract

Background

Breast cancer is the most common malignant tumor among women. Recent studies have found that gut probiotics and their metabolic products play a significant role in activating the immune system, reshaping the tumor microenvironment, and inhibiting cancer progression.

Methods

We established a 4T1 tumor-bearing mice model and analyzed the proportions of CD4⁺ T and CD8⁺ T cells in the spleen using flow cytometry and immunohistochemistry. The expression levels of TNF-α, IL-6, and IL-10 were measured by enzyme-linked immunosorbent assay. Hematoxylin–eosin staining was used to observe the tumor morphology. Selective protein blotting and quantitative real-time PCR were used to analyze the expression of Bax, Bcl-2, and Caspase-3. Cell proliferation was evaluated using the MTT assay, and apoptosis was detected by flow cytometry.

Results

The results indicated that oral administration of CB and AKK possesses the capability to inhibit the progression of 4T1 breast cancer; however, the combined treatment with both strains (CB-AKK) exhibited significantly superior effects compared to each individual strain. Further mechanistic analysis revealed that the CB-AKK combination could activate the antitumor immunity in mice and reshape the tumor microenvironment. Additionally, it was found that the live bacteria and their metabolites derived from CB-AKK could inhibit cell proliferation and promote tumor apoptosis by activating the Bcl-2/Bax signaling pathway.

Conclusion

This study is the first to demonstrate that orally administered live bacteria CB-AKK can inhibit the progression of 4T1 breast cancer, providing a promising new strategy for the development of innovative biotherapies for breast cancer.

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口服联合益生菌丁酸梭菌和嗜粘杆菌通过激活Bcl-2/Bax通路抑制4T1乳腺癌的进展

乳腺癌是女性中最常见的恶性肿瘤。近期研究发现，肠道益生菌及其代谢产物在激活免疫系统、重塑肿瘤微环境、抑制肿瘤进展等方面发挥着重要作用。方法建立4T1荷瘤小鼠模型，采用流式细胞术和免疫组织化学分析脾脏CD4+ T和CD8+ T细胞比例。采用酶联免疫吸附法检测TNF-α、IL-6、IL-10的表达水平。苏木精-伊红染色观察肿瘤形态。采用选择性蛋白印迹和实时荧光定量PCR分析Bax、Bcl-2和Caspase-3的表达。MTT法检测细胞增殖，流式细胞术检测细胞凋亡。结果口服CB和AKK具有抑制4T1乳腺癌进展的作用；然而，两种菌株（CB-AKK）联合处理的效果明显优于单个菌株。进一步的机制分析表明，CB-AKK联合激活小鼠抗肿瘤免疫，重塑肿瘤微环境。此外，我们发现CB-AKK衍生的活菌及其代谢产物可以通过激活Bcl-2/Bax信号通路抑制细胞增殖，促进肿瘤凋亡。结论本研究首次证实口服活菌CB-AKK可以抑制4T1乳腺癌的进展，为乳腺癌创新生物疗法的开发提供了一个有希望的新策略。

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

Cancer Medicine ONCOLOGY-

CiteScore

5.50

自引率

2.50%

发文量

907

审稿时长

19 weeks

期刊介绍： Cancer Medicine is a peer-reviewed, open access, interdisciplinary journal providing rapid publication of research from global biomedical researchers across the cancer sciences. The journal will consider submissions from all oncologic specialties, including, but not limited to, the following areas: Clinical Cancer Research Translational research ∙ clinical trials ∙ chemotherapy ∙ radiation therapy ∙ surgical therapy ∙ clinical observations ∙ clinical guidelines ∙ genetic consultation ∙ ethical considerations Cancer Biology: Molecular biology ∙ cellular biology ∙ molecular genetics ∙ genomics ∙ immunology ∙ epigenetics ∙ metabolic studies ∙ proteomics ∙ cytopathology ∙ carcinogenesis ∙ drug discovery and delivery. Cancer Prevention: Behavioral science ∙ psychosocial studies ∙ screening ∙ nutrition ∙ epidemiology and prevention ∙ community outreach. Bioinformatics: Gene expressions profiles ∙ gene regulation networks ∙ genome bioinformatics ∙ pathwayanalysis ∙ prognostic biomarkers. Cancer Medicine publishes original research articles, systematic reviews, meta-analyses, and research methods papers, along with invited editorials and commentaries. Original research papers must report well-conducted research with conclusions supported by the data presented in the paper.