首页|重组鼠过氧化物还原酶-5体内抗胰腺癌作用研究

重组鼠过氧化物还原酶-5体内抗胰腺癌作用研究

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目的:探讨鼠源重组过氧化物还原酶-5(mPRDX5)在小鼠体内是否具有抗肿瘤活性,从而进一步确证PRDX5的抗肿瘤活性和作用机制.方法:通过体外异源表达和纯化获得高纯度的mPRDX5.小鼠左侧腋背部皮下接种胰腺癌Pan02细胞建立荷瘤小鼠模型.小鼠随机分为PBS(溶剂对照)组、GEM(吉西他滨)50.0 mg/kg组和mPRDX5 10.0 mg/kg组,每组10只,检测小鼠肿瘤相关指标.结果:与PBS组比较,GEM组荷瘤小鼠体质量降低明显,mPRDX5组小鼠体质量有一定程度的增加.PBS组肿瘤生长良好,根据肿瘤体积计算,与PBS组相比,GEM组、mPRDX5 10.0 mg/kg组在D7肿瘤生长抑制率分别为87.07%和52.82%;按瘤重计算,与PBS组相比,GEM组、mPRDX5 10.0 mg/kg组在D7肿瘤生长抑制率分别为95.39%和48.33%.对PBS组和mPRDX5组小鼠肿瘤组织中的巨噬细胞极化状态进行分析,发现相较于PBS组,mPRDX5组小鼠肿瘤组织中表达CD86的M1型巨噬细胞显著增加,而表达CD206的M2型巨噬细胞显著减少.结论:mPRDX5在小鼠体内具有显著的抗胰腺癌活性,且活性的发挥是通过促进肿瘤微环境中的巨噬细胞向M1型极化实现.
Anti-pancreatic cancer effect of recombinant mouse peroxidase reductase-5 in vivo
Objective:To investigate whether murine peroxidase reductase-5(mPRDX5)has anti-tumor activity in mice,so as to further confirm the anti-tumor activity and mechanism of recombinant peroxidase reductase-5.Methods:High purity mPRDX5 was obtained by heterologous expression and purification in vitro.Pancreatic cancer Pan02 cells were inoculated subcutaneously on the left axillary back of mice to establish a tumor bearing mouse model.Mice were randomly divided into PBS(solvent control)group,GEM(gemcitabine)50.0 mg/kg group and mPRDX5 10.0 mg/kg group,with 10 mice in each group,and the tumor related indexes were detected in mice.Results:Compared with PBS group,weight of tumor-bearing mice in GEM group was decreased obviously,while weight of mPRDX5 group was increased to a certain extent.Tumor growth was good in PBS group,according to tumor volume,com-pared with PBS group,tumor growth inhibition rates in D7 were 87.07%in GEM group and 52.82%in mPRDX5 10.0 mg/kg group,re-spectively;according to tumor weight,compared with PBS group,GEM group and mPRDX5 10.0 mg/kg group had tumor growth inhibi-tion rates of 95.39%and 48.33%in D7,respectively.Polarization state of macrophages in tumor tissues of mice in PBS group and mPRDX5 group was analyzed,and it was found that compared with PBS group,M1 macrophages expressing CD86 in tumor tissues of mice in mPRDX5 group were significantly increased,while M2 macrophages expressing CD206 were significantly decreased.Conclu-sion:mPRDX5 has significant anti-pancreatic cancer activity in mice,and the activity is exerted by promoting M1-type polarization of macrophages in the tumor microenvironment.

mPRDX5Protein expressionPancreatic cancerAnti-tumorMacrophage polarization

杨琳、解辉平、王淼、冯佳宁、金媛媛、张志斐、杨兆勇

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华北理工大学药学院,唐山 063000

中国医学科学院医药生物技术研究所,北京 100050

鼠源过氧化物还原酶-5 蛋白表达 胰腺癌 抗肿瘤 巨噬细胞极化

国家自然科学基金中国医科院医学与健康科技创新工程项目

823737672021-I2M-1-070

2024

中国免疫学杂志
中国免疫学会,吉林省医学期刊社

中国免疫学杂志

CSTPCD北大核心
影响因子:0.926
ISSN:1000-484X
年,卷(期):2024.40(5)
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