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:Cnidium officinale polysaccharide enhanced RAW 264.7 cells activation and NK-92 cells cytotoxicity against colon cancer via NF-κB and MAPKs signaling pathways.
Cnidium officinale polysaccharide enhanced RAW 264.7 cells activation and NK-92 cells cytotoxicity against colon cancer via NF-κB and MAPKs signaling pathways.
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本研究从川芎中分离多糖,并研究其免疫增强和抗癌活性。分离得到的粗多糖及其组分F1和F2含有碳水化合物(51.3-63.1%)、硫酸盐(5.4-5.8%)、蛋白质(1.5-7.1%)和糖醛酸(2.1-26.9%)。多糖的分子量(M w)范围为59.9至429.0 × 10 3 g/mol。在RAW 264.7细胞上检测了多糖的免疫刺激活性,结果表明F2处理通过增加NO产生和多种细胞因子的表达,显著增强了RAW 264.7细胞的促炎活性。
此外,利用结肠癌细胞系(HCT-116)研究了多糖处理对NK 细胞(NK-92)抗癌活性的影响。粗多糖及其组分对NK-92和HCT-116细胞均无直接细胞毒性。
然而,F2处理通过上调IFN-γ、TNF-α、NKGp44和granzyme-B的mRNA表达,增强了NK-92细胞对HCT-116细胞的细胞毒性。Western blot结果表明,诱导的RAW 264.7细胞活化和NK-92细胞毒性通过NF-κB和MAPK信号通路发生。
总体而言,川芎来源多糖显示出作为免疫治疗剂的潜力,能够增强促炎巨噬细胞信号传导并激活NK-92细胞;因此,它们可能可用于生物医学应用。
In this study, Cnidium officinale-derived polysaccharides were isolated and investigated for their immune enhancing and anticancer activities. The isolated crude and its fractions, such as F1 and F2, contain carbohydrates (51. 3-63. 1%), sulfates (5. 4-5. 8%), proteins (1. 5-7. 1%), and uronic acids (2. 1-26. 9%).
The molecular weight (M w ) of the polysaccharides ranged from 59. 9 to 429. 0 × 10 3 g/mol. The immunostimulatory activity of the polysaccharides was tested on RAW 264. 7 cells, and the results showed that the F2 treatment notably enhanced pro-inflammatory activity in RAW 264. 7 cells by increasing NO production and the expression of various cytokines.
Furthermore, the influence of polysaccharide treatment on natural killer cells (NK-92) anticancer activities was investigated using a colon cancer cell line (HCT-116). Crude polysaccharide and its fractions showed no direct cytotoxicity to NK-92 and HCT-116 cells.
However, the treatment of F2 showed an enhancement of NK-92 cells cytotoxicity against HCT-116 cells by upregulating the mRNA expression of IFN-γ, TNF-α, NKGp44, and granzyme-B. The western blot results showed that the induced RAW 264. 7 cells activation and NK-92 cells cytotoxicity occur via NF-κB and MAPK signaling pathways.
Overall, C. officinale-derived polysaccharides show potential as immunotherapeutic agents capable of enhancing pro-inflammatory macrophage signaling and activating NK-92 cells; thus, they could be useful for biomedical applications.
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