蝎毒多肽提取物对肿瘤微环境中树突状细胞成熟表型的影响  

Effect of PESV on dendritic cells maturation in the tumor microenvironment

作　　者：张月英[1,2] 张维东[1,2] 武利存[1,2] 王朝霞[1,2] 王兆朋[1,2] 贾青[1,2] 徐林[1,2] 张俊平[1,2] 

机构地区：[1]山东省医学科学院基础医学研究所 [2]山东省现代医用药物与技术重点实验室山东省医学科学院,济南250062

出　　处：《山东大学学报（医学版）》2010年第10期34-38,共5页Journal of Shandong University:Health Sciences

基　　金：国家自然科学基金资助项目(30873408);山东省自然科学基金资助项目(ZR2009CL030;Y2007C094;Y2008C176);山东省科技攻关项目(2008GG30002067;2008GG2NS02023)

摘　　要：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 mechanism of PESV（polypeptide extract from scorpion venom） on promotion of dendritic cells maturation in the tumor microenvironment.Methods Lewis lung cancer models were established by subcutaneously implanting Lewis lung cells into C57BL/6 mice.The tumor-bearing mice were randomly divided into 3 groups： the control group,the chemotherapy group（treated with CTX） and the experimental group（treated with PESV between courses of chemotherapy）.There were 8 mice in each group.PESV was intrinsically injected for 21 days in the experimental group.Then,the volume of tumors was evaluated every two days,and the tumor growth curve was recorded.Flow cytometry（FCM） was applied to detect expression of CD80 and CD83in dendritic cells.VEGF and TGF-β1 were determined by imunohistochemical assay and RT-PCR.Results After21days treatment of PESV and chemotherapy,tumor growth was inhibited in the experimental group.Compared with the control,the number of TIDC and expression of CD80 increased,but expression of VEGF and TGF-β1 was down-regulated.Conclusions PESV can promote dendritic cells maturation through inhibition of VEGF and TGF-β1 expression in the tumor microen-vironment during the interval of chemotherapy.

关 键 词：蝎毒多肽 肿瘤浸润树突状细胞 血管内皮生长因子 肿瘤生长转化因子β1 LEWIS肺癌 模型 动物 小鼠 

分 类 号：R979.1[医药卫生—药品] R-332[医药卫生—药学]