ZhenQi FuZheng formula inhibits the growth of colorectal tumors by modulating intestinal microflora-mediated immune function

Weiqi Meng, Zhiping Li, Yiting Zhang, Anhui Yang, Yanzhen Wang, Yulin Zhou, Wanyue Wu, Ye Qiu, Lanzhou Li
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Abstract

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-Apcem1Cin(MinC)/Gpt (ApcMin/+) 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 ApcMin/+ 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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贞芪扶正方通过调节肠道菌群介导的免疫功能抑制结直肠肿瘤的生长
贞芪扶正方具有免疫系统调节功能和潜在的抗肿瘤生物活性,主要成分为黄芪和女贞。在炎症细胞和B6/JGpt-Apcem1Cin(MinC)/Gpt (ApcMin/+)小鼠中分析ZQFZ对结直肠癌肿瘤生长的抑制作用。ZQFZ通过降低脂多糖诱导的RAW264.7细胞中核因子κB (NF-κB)通路相关蛋白的磷酸化而表现出抗炎活性。治疗56 d后,ZQFZ缓解了ApcMin/+小鼠的结直肠癌(CRC)进展,增加了ApcMin/+小鼠的体重和胸腺指数。对肠道菌群的分析表明,ZQFZ影响某些免疫相关细菌的丰度,这可能解释了其免疫调节作用。外周血中T细胞和NK细胞的比例显著升高,血清或结肠或两者中15种免疫相关细胞因子受到调节。ZQFZ上调脾脏和结直肠肿瘤中CD4和CD8水平,降低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,促进抗肿瘤免疫应答,抑制结直肠癌的发生发展。本研究为ZQFZ作为结直肠癌治疗剂的应用提供了实验依据。
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