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来自 的葡聚糖通过调节巨噬细胞极化和WNT/β-连环蛋白信号通路抑制乳腺癌的增殖和转移。

Glucan from suppresses breast cancer proliferation and metastasis by regulating macrophage polarization and the WNT/β-catenin signaling pathway.

作者信息

Alitongbieke Gulimiran, Zhang Xiuru, Zhu Fukai, Wu Qici, Lin Zhichao, Li Xiumin, Xue Yu, Lai Xuebin, Feng Jiexin, Huang Rongjie, Pan Yutian

机构信息

Engineering Technological Center of Mushroom Industry, Minnan Normal University, Zhangzhou, Fujian 363000, People's Republic of China.

Department of Breast Surgery, Zhangzhou Affiliated Hospital of Fujian Medical University, Zhangzhou, Fujian 363099, People's Republic of China.

出版信息

J Cancer. 2024 Jan 1;15(5):1169-1181. doi: 10.7150/jca.89873. eCollection 2024.

DOI:10.7150/jca.89873
PMID:38356709
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10861828/
Abstract

The glucan extract of () has multiple biological properties, similar to extracts of other natural edible fungi. Drugs traditionally used in cancer treatment are associated with several drawbacks, such as side effects, induction of resistance, and poor prognosis, and many recent studies have focused on polysaccharides extracted from natural sources as alternatives. Our study focuses on the therapeutic role and molecular mechanism of action of in breast cancer progression. MMTV-PyMT transgenic mice were used as the spontaneous breast cancer mice model. Immunoblotting, hematoxylin-eosin staining, immunohistochemistry, and immunofluorescence were used to evaluate the tumor behaviors in breast cancer. The inflammatory cell model was constructed using TNF-α. Macrophage activation and WNT/β-catenin signaling were assayed using western blotting and immunofluorescence. management significantly inhibited tumor growth and promoted tumor cell apoptosis in MMTV-PyMT transgenic mice. Besides, the challenge also attenuated the ability of breast tumors to metastasize into lung tissues. Mechanistically, treatment restrained the polarization of M1 macrophages to M2 macrophages and suppressed WNT/β-catenin signaling in mouse tumor tissues, which implied that -mediated tumor inhibition partly occurred regulating the inflammatory response. Findings from experiments confirmed that inhibited the TNF-α-induced nuclear transportation of β-catenin, thus preventing inflammation signaling and the expression of c-Myc in MCF-7 cells. inhibits breast cancer growth and metastasis by regulating macrophage polarization and the WNT/β-catenin signaling axis. The findings of this study suggest that may be a promising therapeutic strategy for breast cancer.

摘要

()的葡聚糖提取物具有多种生物学特性,类似于其他天然可食用真菌的提取物。传统上用于癌症治疗的药物存在若干缺点,如副作用、诱导耐药性和预后不良,最近许多研究聚焦于从天然来源提取的多糖作为替代物。我们的研究聚焦于(该提取物)在乳腺癌进展中的治疗作用及分子作用机制。MMTV-PyMT转基因小鼠被用作自发性乳腺癌小鼠模型。采用免疫印迹法、苏木精-伊红染色、免疫组织化学和免疫荧光法来评估乳腺癌中的肿瘤行为。使用TNF-α构建炎症细胞模型。采用蛋白质免疫印迹法和免疫荧光法检测巨噬细胞活化及WNT/β-连环蛋白信号传导。(该提取物)处理显著抑制了MMTV-PyMT转基因小鼠的肿瘤生长并促进了肿瘤细胞凋亡。此外,(该提取物)刺激还减弱了乳腺肿瘤转移至肺组织的能力。从机制上来说,(该提取物)处理抑制了M1巨噬细胞向M2巨噬细胞的极化,并抑制了小鼠肿瘤组织中的WNT/β-连环蛋白信号传导,这表明(该提取物)介导的肿瘤抑制部分是通过调节炎症反应发生的。(体外)实验结果证实,(该提取物)抑制了TNF-α诱导的β-连环蛋白的核转运,从而阻止了炎症信号传导及MCF-7细胞中c-Myc的表达。(该提取物)通过调节巨噬细胞极化和WNT/β-连环蛋白信号轴来抑制乳腺癌的生长和转移。本研究结果表明,(该提取物)可能是一种有前景的乳腺癌治疗策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d649/10861828/676148f93e9d/jcav15p1169g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d649/10861828/ed83d3b8f43b/jcav15p1169g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d649/10861828/e15fea7fa6a1/jcav15p1169g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d649/10861828/0560d0d7bf99/jcav15p1169g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d649/10861828/efb8f908f693/jcav15p1169g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d649/10861828/4175417bb23a/jcav15p1169g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d649/10861828/676148f93e9d/jcav15p1169g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d649/10861828/ed83d3b8f43b/jcav15p1169g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d649/10861828/e15fea7fa6a1/jcav15p1169g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d649/10861828/0560d0d7bf99/jcav15p1169g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d649/10861828/efb8f908f693/jcav15p1169g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d649/10861828/4175417bb23a/jcav15p1169g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d649/10861828/676148f93e9d/jcav15p1169g006.jpg

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