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目的探讨蝎毒多肽提取物诱导肿瘤微环境中树突状细胞成熟的分子机制。方法建立小鼠Lew is肺癌皮下荷瘤模型,随机分为荷瘤对照组、化疗组(CTX组)和实验组(CTX+PESV组),每组8只。实验组在常规化疗的间隔期给予蝎毒多肽提取物干预,连续治疗21d,记录肿瘤生长曲线,观察蝎毒多肽提取物对肿瘤浸润性树突状细胞成熟表型的影响,并采用实时荧光定量PCR和免疫组织化学检测肿瘤微环境中血管内皮生长因子(VEGF)和肿瘤生长转化因子β1(TGF-β1)的表达变化,从肿瘤组织微环境的角度探讨其作用机制。结果常规化疗的间隔期给予蝎毒多肽提取物连续治疗21d后,实验组中Lew is肺癌移植瘤的生长明显受到抑制(P<0.05);肿瘤浸润性树突状细胞数量以及CD80表达均较模型组升高(P<0.05);与荷瘤对照组比较,化疗组和实验组肿瘤微环境中VEGF mRNA的相对表达量降低,分别为荷瘤对照组的32%和12%;TGF-β1mRNA表达量也降低,分别是荷瘤对照组的42%和21%(P<0.05)。结论蝎毒多肽提取物在化疗间期通过抑制肿瘤微环境中VEGF和TGF-β1的表达,促进树突状细胞的成熟,恢复其功能表型。
Objective To explore the molecular mechanism of polypeptide extract of scorpion venom inducing dendritic cell maturation in tumor microenvironment. Methods The mouse Lew is lung cancer subcutaneous tumor model was established and randomly divided into tumor-bearing control group, chemotherapy group (CTX group) and experimental group (CTX + PESV group), with 8 mice in each group. The experimental group was treated with extract of scorpion venom polypeptide at the interval of routine chemotherapy for 21 days. The growth curve was recorded and the effect of scorpion venom peptide extract on the maturation phenotype of tumor-infiltrating dendritic cells was observed. The real-time fluorescence quantitative PCR and immunohistochemistry were used to detect the expression of vascular endothelial growth factor (VEGF) and tumor growth transforming factor-β1 (TGF-β1) in tumor microenvironment, and to explore its mechanism from the perspective of tumor microenvironment. Results The results showed that the growth of Lewis lung cancer xenografts in experimental group was significantly inhibited (P <0.05) after 21 days of continuous treatment with the scorpion venom peptide extract at the interval of routine chemotherapy. The number of tumor-infiltrating dendritic cells and the expression of CD80 (P <0.05). Compared with the tumor-bearing control group, the relative expression of VEGF mRNA in the tumor microenvironment of the chemotherapy group and the experimental group was decreased by 32% and 12% respectively in the tumor-bearing control group; the expression of TGF-β1 mRNA The amounts also decreased, 42% and 21%, respectively, of the tumor-bearing control group (P <0.05). Conclusion Scorpion venom peptide extract can promote dendritic cell maturation and restore its functional phenotype by inhibiting the expression of VEGF and TGF-β1 in the tumor microenvironment during chemotherapy.