RNF43 p.G659fs 通过 PI3K/AKT/mTOR 信号通路和 HLA-E 上调导致 MSI-high 结直肠癌中 NK 细胞功能障碍
RNF43 p.G659fs leads to natural killer cell dysfunction in MSI-high colorectal cancer through PI3K/AKT/mTOR signaling and HLA-E up-regulation.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Anticancer Effects of the Polysaccharide Fraction of Bioprocessed Black Rice Bran Extract in Triple-Negative Breast Cancer (TNBC) Cells and Radiotherapy-Resistant TNBC Cells by Inhibiting Interactions with Endothelial Cells and Inducing Natural Killer Cell Activity.
Anticancer Effects of the Polysaccharide Fraction of Bioprocessed Black Rice Bran Extract in Triple-Negative Breast Cancer (TNBC) Cells and Radiotherapy-Resistant TNBC Cells by Inhibiting Interactions with Endothelial Cells and Inducing Natural Killer Cell Activity.
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肿瘤微环境由内皮细胞(ECs)和免疫细胞等成分组成,在癌症进展、治疗耐药和转移中发挥关键作用。癌细胞与内皮的黏附、跨内皮迁移以及癌细胞免疫逃逸促进了这些过程。
在本研究中,我们研究了源自生物加工黑米糠提取物的富含多糖组分(BRB-F-P)对三阴性乳腺癌(TNBC)和放疗耐药TNBC(RT-R-TNBC)细胞与ECs相互作用的影响,以及对自然杀伤(NK)细胞溶细胞功能的影响。BRB-F-P处理不影响ECs、TNBC或RT-R-TNBC细胞的活力。
然而,BRB-F-P(50和100 g/mL)显著抑制了TNBC和RT-R-TNBC细胞的克隆形成能力,并减弱了ATP诱导的ECs中血管黏附分子-1、细胞间黏附分子-1和Vimentin的表达,以及血管内皮钙黏蛋白的磷酸化。
此外,BRB-F-P显著减少了癌细胞对ECs的黏附,并抑制了其穿过ECs迁移的能力。有趣的是,BRB-F-P通过诱导颗粒酶B释放和下调靶癌细胞中人类白细胞抗原-E的表达,增强了NK细胞介导的对TNBC和RT-R-TNBC细胞的细胞毒性。这些结果表明,BRB-F-P通过抑制与ECs的相互作用并诱导NK细胞活性,在TNBC和RT-R-TNBC中发挥抗癌作用,且不具有细胞毒性。
The tumor microenvironment, comprising elements such as endothelial cells (ECs) and immune cells, plays a critical role in cancer progression, therapy resistance, and metastasis. Adhesion of cancer cells to the endothelium, their transendothelial migration, and immune evasion by cancer cells contribute to these processes.
In this study, we investigated the effect of the polysaccharide-rich fraction derived from bioprocessed black rice bran extract (BRB-F-P) on the interaction between triple-negative breast cancer (TNBC) and radiotherapy-resistant TNBC (RT-R-TNBC) cells with ECs, as well as on the cytolytic function of natural killer (NK) cells. BRB-F-P treatment did not affect the viability of ECs, TNBC, or RT-R-TNBC cells.
However, BRB-F-P (50 and 100 g/mL) significantly suppressed the clonogenicity of TNBC and RT-R-TNBC cells and attenuated ATP-induced expression of vascular adhesion molecule-1, intercellular adhesion molecule-1, and Vimentin, along with the phosphorylation of vascular endothelial cadherin in ECs.
Additionally, BRB-F-P markedly reduced cancer cell adhesion to ECs and inhibited their ability to transmigrate through ECs. Interestingly, BRB-F-P increased NK cell-mediated cytotoxicity against TNBC and RT-R-TNBC cells by inducing granzyme B release and downregulating human leukocyte antigen-E expression in target cancer cells. These results suggest that BRB-F-P exerts anticancer effects in TNBC and RT-R-TNBC by inhibiting interactions with ECs and inducing NK cell activity without cytotoxicity.
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