Engineering Technological Center of Mushroom Industry, School of Biological Science and Biotechnology, Minnan Normal University, Zhangzhou, Fujian, People's Republic of China.
Breast Surgery Department, Zhangzhou Hospital of Fujian Medical University, Zhangzhou, Fujian, People's Republic of China.
Immun Inflamm Dis. 2023 May;11(5):e876. doi: 10.1002/iid3.876.
β-Glucan from Lentinus edodes (LNT), an edible mushroom, possesses strong anticancer activity. However, the therapeutic effects of LNT during the occurrence and progression of breast cancer and their underlying molecular mechanisms have not been elucidated.
Mouse mammary tumor virus-polyoma middle tumor-antigen (MMTV-PyMT) transgenic mice were used as a breast cancer mouse model. Hematoxylin and eosin, immunohistochemical, and immunofluorescence staining were performed for histopathological analysis. Moreover, we developed an inflammatory cell model using tumor necrosis factor-α (TNF-α). Macrophage polarization was assessed using western blot analysis and immunofluorescence.
Orphan nuclear receptor 77 (Nur77) and sequestosome-1 (p62) were highly expressed and positively correlated with each other in breast cancer tissues. LNT significantly inhibited tumor growth, ameliorated inflammatory cell infiltration, and induced tumor cell apoptosis in PyMT transgenic mice. Moreover, LNT attenuated the ability of tumors to metastasize to lung tissue. Mechanistically, LNT treatment restrained macrophage polarization from M1 to M2 phenotype and promoted autophagic cell death by inhibiting Nur77 expression, AKT/mTOR signaling, and inflammatory signals in breast tumor cells. However, LNT did not exhibit a direct pro-autophagic effect on tumor cell death, except for its inhibitory effect on Nur77 expression. LNT-mediated autophagic tumor cell death depends on M1 macrophage polarization. In in vitro experiments, LNT inhibited the upregulation of p62, autophagy activation, and inflammatory signaling pathways in Nur77 cells.
LNT inhibited macrophage M2 polarization and subsequently blocked the AKT/mTOR and inflammatory signaling axes in breast cancer cells, thereby promoting autophagic tumor cell death. Thus, LNT may be a promising therapeutic strategy for breast cancer.
香菇（Lentinus edodes）β-葡聚糖（LNT）是一种食用蘑菇，具有很强的抗癌活性。然而，LNT 在乳腺癌发生和发展过程中的治疗效果及其潜在的分子机制尚未阐明。
利用鼠乳腺肿瘤病毒-多瘤病毒中肿瘤抗原（MMTV-PyMT）转基因小鼠作为乳腺癌小鼠模型。进行苏木精和伊红、免疫组织化学和免疫荧光染色以进行组织病理学分析。此外，我们使用肿瘤坏死因子-α（TNF-α）建立了炎症细胞模型。使用 Western blot 分析和免疫荧光评估巨噬细胞极化。
孤儿核受体 77（Nur77）和自噬体相关蛋白 1（p62）在乳腺癌组织中高表达，且呈正相关。LNT 显著抑制 PyMT 转基因小鼠的肿瘤生长，减轻炎症细胞浸润，并诱导肿瘤细胞凋亡。此外，LNT 减弱了肿瘤向肺组织转移的能力。在机制上，LNT 通过抑制 Nur77 表达、AKT/mTOR 信号和乳腺癌细胞中的炎症信号，抑制巨噬细胞从 M1 向 M2 表型极化，并促进自噬性细胞死亡。然而，LNT 除了抑制 Nur77 表达外，对肿瘤细胞死亡没有直接的促进自噬作用。LNT 介导的自噬性肿瘤细胞死亡依赖于 M1 巨噬细胞极化。在体外实验中，LNT 抑制了 Nur77 细胞中 p62 的上调、自噬激活和炎症信号通路。
LNT 抑制巨噬细胞 M2 极化，进而阻断乳腺癌细胞中的 AKT/mTOR 和炎症信号轴，从而促进自噬性肿瘤细胞死亡。因此，LNT 可能是一种有前途的乳腺癌治疗策略。
