文章摘要
黄芪颗粒联合PD-1抑制剂调控免疫功能抑制胃癌的作用机制研究
Mechanisms of Astragalus Granules Combined with a PD-1 Inhibitor in Modulating Immune Function and Suppressing Gastric Cancer Xenografts
DOI:
中文关键词: 黄芪颗粒  PD-1抑制剂  免疫功能  胃癌  作用机制
英文关键词: Astragalus granules  PD-1 inhibitor  immune modulation  gastric cancer  mechanisms
基金项目:
作者单位邮编
崔静 福建医科大学附属第一医院 350005
陈永浩 福建医科大学附属第一医院 
吴天敏* 福建医科大学附属第一医院 
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中文摘要:
      目的 探讨黄芪颗粒联合PD-1抑制剂对胃癌移植瘤的抑制作用及其免疫学机制。方法 将MKN-45人胃癌细胞接种于BALB/c裸鼠,随机分为模型组、PD-1抑制剂组、黄芪颗粒组和联合组,每组6只。黄芪颗粒组每日灌胃,PD-1抑制剂组按周期注射替雷利珠单抗,联合组同步给予两种干预。干预9周后,评估裸鼠一般状况、瘤体质量及体积,并检测血清细胞因子水平及肿瘤组织免疫细胞比例。结果 与模型组相比,干预组裸鼠活动评分明显提高,且联合组裸鼠活动评分更显著高于 PD-1 抑制剂组与黄芪颗粒组(P<0.05);肿瘤质量与体积显著降低(P<0.05)。其中,联合组抑瘤率最高(71.49%),其瘤体质量与体积显著低于PD-1抑制剂组和黄芪颗粒组(P<0.05)。在免疫学指标方面,联合组肿瘤组织CD8?T细胞和NK细胞比例显著升高,血清IL-6和TGF-β1水平显著降低(P<0.05);同时,黄芪颗粒可维持血清IL-2水平稳定,仅 PD-1 抑制剂组血清 IL-2 水平较模型组显著降低(P<0.05),黄芪颗粒组与联合组裸鼠血清 IL-2 水平则未出现统计学差异(P>0.05)。结论 黄芪颗粒联合PD-1抑制剂在抑制胃癌移植瘤方面优于单药干预,其机制可能与增强效应性T细胞和NK细胞活性、改善炎症性肿瘤微环境及维持免疫效应信号相关。本研究为黄芪颗粒辅助免疫治疗胃癌提供了实验依据。
英文摘要:
      Objective: This study aimed to evaluate the inhibitory effects of Astragalus granules in combination with a PD-1 inhibitor on gastric cancer xenografts and to elucidate the underlying immunological mechanisms. Methods: Human gastric cancer MKN-45 cells were subcutaneously inoculated into BALB/c nude mice, which were randomly divided into four groups (n = 6 per group): the model group, PD-1 inhibitor group, Astragalus granules group, and combination group. Astragalus granules were administered daily via oral gavage, while the PD-1 inhibitor (Tislelizumab) was delivered intraperitoneally according to treatment cycles. The combination group received both treatments concurrently. After nine weeks, general conditions, tumor weight and volume, serum cytokine concentrations, and immune cell proportions in tumor tissues were evaluated. Results: Compared with the model group, all treatment groups showed significantly higher activity scores and reduced tumor weight and volume (P < 0.05). The combination group exhibited the greatest tumor inhibition rate (71.49%), with tumor weight and volume significantly lower than those in either monotherapy group (P < 0.05). Immunological analyses indicated that the combination group had markedly increased proportions of CD8? T cells and NK cells in tumor tissues, accompanied by significantly reduced serum IL-6 and TGF-β1 levels (P < 0.05). Furthermore, Astragalus granules helped maintain stable serum IL-2 levels, in contrast to the decrease observed in the PD-1 inhibitor group. Conclusion: The combination of Astragalus granules with a PD-1 inhibitor produced superior anti-tumor effects compared with monotherapy in gastric cancer xenografts. The enhanced efficacy may result from the activation of CD8? T-cell and NK-cell responses, improvement of the inflammatory tumor microenvironment, and preservation of key immune signaling pathways. These findings provide experimental evidence supporting Astragalus granules as a promising adjuvant in gastric cancer immunotherapy.
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