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:Development of a compound herbal formulation (HBK) with antitumor and antioxidant functions for cancer adjuvant therapy.
Development of a compound herbal formulation (HBK) with antitumor and antioxidant functions for cancer adjuvant therapy.
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本研究全面评估了一种基于中药的多种草药复方在肺癌中的免疫调节与抗氧化作用。
癌症仍是全球主要死亡原因,转移、复发和治疗耐药等问题持续存在。中医药与现代生物医学整合显示出提高治疗效果的潜力。肿瘤微环境(TME),尤其是其中的免疫环境,在癌症进展中发挥关键作用。
本研究探究由17种草药和食物组成的配方HBK是否具有调节TME并增强抗肿瘤免疫的潜力。
在BALB/c肺癌模型中,L1肿瘤荷瘤小鼠分别喂食添加HBK的饲料或对照饲料。测量肿瘤生长、血清细胞因子和抗氧化酶,并通过流式细胞术、RNA测序和Western blot分析肿瘤及脾脏。
HBK含有β-葡聚糖、黄酮和多酚等多种具有免疫调节作用的生物活性成分。在小鼠肺癌模型中,HBK治疗显著抑制肿瘤生长并减少肺转移。HBK治疗组小鼠血清抗氧化酶(超氧化物歧化酶、谷胱甘肽过氧化物酶)和关键抗肿瘤细胞因子(IL-12、IL-2、IFN-γ、MIP-1α)水平显著升高。TME分析显示免疫环境向抗肿瘤方向转变,具体表现为促肿瘤免疫细胞(MDSC、Th2、Th17、M2巨噬细胞和Treg)减少,细胞毒性NK细胞和CD8 T细胞增加。RNA测序发现NK细胞活化及趋化因子信号通路上调;Western blot显示治疗组肿瘤中NF-κB和TLR3通路下调。
本研究全面评估了基于中医药的多草药配方在肺癌中的免疫调节和抗氧化作用。HBK显著增强抗肿瘤免疫、提高抗氧化酶和细胞因子活性,并重塑TME。值得注意的是,这些作用由抑制TLR3/NF-κB信号通路介导。尽管既往研究已将单味药物与该通路联系起来,我们的研究首次证明中医多草药配方可在体内通过抑制TLR3/NF-κB来调节肿瘤免疫。
Cancer remains a leading cause of global mortality, with challenges such as metastasis, recurrence, and therapy resistance. Integrating traditional Chinese medicine with modern biomedicine has demonstrated the potential to enhance treatment efficacy. The tumor microenvironment (TME), particularly its immune landscape, plays a crucial role in cancer progression.
This study investigated HBK, a formulation of seventeen herbs and foods, for its potential to modulate the TME and boost antitumor immunity.
In a BALB/c lung cancer model, L1 tumor-bearing mice were fed either HBK-supplemented or control chow. Tumor growth, serum cytokines, and antioxidant enzymes were measured. Tumors and spleens were analyzed by flow cytometry, RNA sequencing, and Western blotting.
HBK contains various bioactive compounds, including -glucans, flavonoids, and polyphenols, which are known for their immunomodulatory properties. In a murine lung cancer model, HBK treatment significantly inhibited tumor growth and reduced lung metastasis. Serum levels of antioxidant enzymes (superoxide dismutase, glutathione peroxidase) and key antitumor cytokines (IL-12, IL-2, IFN- , MIP-1 ) were significantly increased in HBK-treated mice. TME analysis revealed a shift toward an anti-tumor immune landscape, characterized by a reduction in pro-tumor immune cells (MDSCs, Th2, Th17, M2 macrophages, and Tregs) and an increase in cytotoxic natural killer (NK) and CD8 T cells. RNA-Seq analysis identified upregulation of NK cell activation and chemokine signaling pathways, whereas Western blot analysis revealed downregulation of NF- B and TLR3 pathways in the treated tumors.
This study provides a comprehensive evaluation of a TCM-based multi-herb formulation for its immunomodulatory and antioxidant effects in lung cancer. HBK significantly enhanced anti-tumor immunity, increased antioxidant enzyme and cytokine activity, and remodeled the tumor microenvironment. Notably, these effects were mediated through inhibition of the TLR3/NF- B signaling pathway. While individual herbal components have previously been linked to this pathway, our study is the first to demonstrate that a TCM-based multi-herb formula can modulate tumor immunity via TLR3/NF- B inhibition in vivo.
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