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:ZhenQi FuZheng formula inhibits the growth of colorectal tumors by modulating intestinal microflora-mediated immune function.
ZhenQi FuZheng formula inhibits the growth of colorectal tumors by modulating intestinal microflora-mediated immune function.
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贞芪扶正方(ZQFZ)的主要成分是黄芪和女贞子,具有免疫系统调节功能和潜在的抗肿瘤生物活性。本研究在炎症细胞和B6/JGpt-Apc em1Cin(MinC)/Gpt(Apc Min/+)小鼠中分析了ZQFZ对结直肠肿瘤生长的抑制作用。ZQFZ在脂多糖诱导的RAW264.7细胞中通过降低核因子-κB(NF-κB)通路相关蛋白的磷酸化而表现出抗炎活性。治疗56天后,ZQFZ减轻了结直肠癌(CRC)的进展,并增加了Apc Min/+小鼠的体重和胸腺指数值。肠道菌群分析显示,ZQFZ影响了某些免疫相关细菌的丰度,这可能解释其免疫调节作用。
此外,外周血中T细胞和NK细胞的百分比显著增加,血清或结肠或两者中15种免疫相关细胞因子受到调控。ZQFZ上调了脾脏和结直肠肿瘤中CD4和CD8的水平,并降低了结直肠肿瘤中细胞毒性T淋巴细胞相关蛋白4和程序性死亡配体1的表达水平。ZQFZ通过调节免疫系统促进抗肿瘤免疫反应并抑制CRC的发生和发展。本研究为ZQFZ作为CRC治疗药物的应用提供了实验依据。
Zhenqi Fuzheng formula (ZQFZ), of which the main ingredients are Astragalus membranaceus and Ligustrum lucidum , has immune system regulatory functions and potential anti-tumor bioactivity. The inhibition of colorectal tumor growth by ZQFZ was analyzed in inflammatory cells and B6/JGpt- Apc em1Cin(MinC) /Gpt ( Apc Min/+ ) mice. ZQFZ exhibited anti-inflammatory activity by decreasing the phosphorylation of nuclear factor-kappa B (NF-κB) pathway-related proteins in lipopolysaccharide-induced RAW264.
7 cells. After 56 days of treatment, ZQFZ alleviated the progression of colorectal cancer (CRC) and increased the body weight and thymic index values of the Apc Min/+ mice. An analysis of the intestinal microflora showed that ZQFZ affected the abundance of certain immune-related bacteria, which may explain its immunomodulatory effects.
Moreover, the percentages of T cells and NK cells in peripheral blood were significantly increased and 15 immune-related cytokines were regulated in serum or the colon or both. ZQFZ upregulated the levels of CD4 and CD8 in the spleen and colorectal tumors and decreased the expression levels of cytotoxic T-lymphocyte-associated protein 4 and programmed death-ligand 1 in colorectal tumors. ZQFZ promoted an anti-tumor immune response and inhibited the occurrence and development of CRC by regulating the immune system.
This study provides the experimental basis for the application of ZQFZ as a therapeutic agent for CRC.
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