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:Immunoregulatory Effects of Codonopsis pilosula Polysaccharide Modified Selenium Nanoparticles on H22 Tumor-Bearing Mice.
Immunoregulatory Effects of Codonopsis pilosula Polysaccharide Modified Selenium Nanoparticles on H22 Tumor-Bearing Mice.
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党参多糖(CPP)和稀有元素硒(Se)已被证实具有多种生物活性;我们此前研究显示,CPP修饰硒纳米颗粒(CPP-SeNP)在体外具有显著增强的肿瘤细胞毒作用。
本研究旨在探讨CPP-SeNP复合物通过增强免疫抑制H22实体瘤的作用。研究建立H22荷瘤小鼠模型,并通过评估各组细胞因子表达、免疫细胞活性及肿瘤细胞凋亡指标,进一步探索CPP-SeNP的潜在抗肿瘤机制。
结果显示,CPP-SeNP在体内对荷瘤小鼠免疫器官具有有效的剂量依赖性保护作用,可增加外周白细胞计数并抑制实体瘤生长;高剂量组(1.5 mg/kg)抑瘤率为47.18%。
此外,CPP-SeNP处理显著提高小鼠血清TNF-α、IFN-γ和IL-2水平,增强NK细胞细胞毒性和巨噬细胞吞噬能力,并增加淋巴细胞亚群数量及其增殖活性。CPP-SeNP通过上调实体瘤中的Bax表达、下调Bcl-2表达,改善免疫系统清除肿瘤细胞的能力,提示其可能激活线粒体凋亡通路。
因此,CPP-SeNP可通过增强荷瘤小鼠的免疫应答有效抑制肿瘤生长,这可能与其调节肠道菌群短链脂肪酸代谢有关。这些发现可为进一步开发CPP-SeNP作为功能性食品和药物佐剂提供理论支持和数据基础。
Codonopsis pilosula polysaccharide (CPP) and rare element selenium (Se) have been proved to exert various biological activities, and our previous study demonstrated that selenium nanoparticles modified with CPP (CPP-SeNPs) possessed significantly enhanced tumor cytotoxicity in vitro.
This study aimed to investigated the inhibitory effects of CPP-SeNPs complex on H22 solid tumors via immune enhancement. In this study, the H22 tumor-bearing mice model was constructed, and the potential mechanisms of CPP-SeNPs antitumor effects were further explored by evaluating cytokines expression levels, immune cells activities and tumor cells apoptotic indicators in each group.
The results demonstrated that CPP-SeNPs effectively exerted dose-dependent protective effects on the immune organs of tumor-bearing mice in vivo, leading to increase in peripheral white blood cell counts and inhibition of solid tumor growth with inhibitory rate of 47. 18% in high-dose group (1. 5 mg/kg).
Furthermore, CPP-SeNPs treatment significantly elevated the levels of TNF- , IFN- , and IL-2 in mice sera, enhanced NK cell cytotoxicity, augmented macrophage phagocytosis capacity, as well as increased both the amounts and proliferation activity of lymphocyte subsets. CPP-SeNPs improved the immune system's ability to clear tumor cells by up-regulating Bax expression while down-regulating Bcl-2 expression within solid tumors, indicating the potential activation of mitochondrial apoptosis pathway.
Therefore, CPP-SeNPs administration can effectively inhibit tumor growth by enhancing immune response in tumor-bearing mice, which might be relevant to the regulation of gut microbiota short-chain fatty acids metabolisms.
These findings could provide theoretical support and data foundation for further development of CPP-SeNPs as functional food and drug adjuvants.
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