治疗用卡介苗抑瘤小鼠模型的建立及其作用机制研究
A Tumor-suppressor Mouse Model of BCG for Therapeutic Use and Mechanisms
孙礼进 1朱战 1王璐 1徐守腾 1陈浩伟 1张健 1江秋虹 1陶立峰1
作者信息
- 1. 230088 安徽合肥,安徽智飞龙科马生物制药有限公司研发中心
- 折叠
摘要
目的 探讨治疗用卡介苗对小鼠膀胱癌细胞的体内抑制作用.方法 将治疗用卡介苗菌悬液与小鼠膀胱癌细胞悬液等体积混合,皮下接种C57BL/6J小鼠,3周后,取皮下实体瘤,称重计算抑瘤率;同时取C57BL/6J小鼠脾脏,酶联免疫斑点试验检测分泌抗原特异性干扰素γ、白介素2细胞斑点数.结果 不同浓度治疗用卡介苗组的瘤体质量均显著低于模型对照组(P=0.000),当治疗用卡介苗为10 mg·ml-1 和5 mg·ml-1 时,肿瘤生长抑制率均高于90%,当治疗用卡介苗为2.5 mg·ml-1 时,肿瘤生长抑制率均高于70%,呈明显的剂量依赖性;且干扰素γ、白介素2细胞斑点数均显著高于模型对照组(P=0.000).结论 成功建立了治疗用卡介苗皮下抑瘤小鼠模型,其抗肿瘤作用的产生可能是通过激活Th1型免疫反应提高细胞分泌干扰素γ和白介素2的水平,从而促进细胞介导的免疫应答.
Abstract
Objective To investigate the in vivo inhibitory effect of bacillus Calmette-Guérin(BCG)for therapeu-tic use against mouse bladder cancer cells.Methods The bacterial suspension of BCG for therapeutic use was mixed with mouse bladder cancer cell suspension of the same volume before being subcutaneously inoculated with C57BL/6J mice.After 3 weeks,the subcutaneous solid tumors were taken and weighed to calculate the tumor inhibition rate.Meanwhile,the spleens of C57BL/6J mice were taken,the numbers of spots of secreted antigen-specific interferon-γ(IFN-γ)and inter-leukin-2(IL-2)cells were detected using the enzyme linked immunospot assay method.Results The tumors in the BCG for therapeutic use group were much lighter than those in the model control group.The rate of tumor growth inhibition exceeded 90%when BCG for therapeutic use was 10 mg·ml-1 and 5 mg·ml-1 and was above 70%when BCG was 2.5 mg·ml-1,suggesting significant dose dependence.IFN-γ and IL-2 cell spots in this group far outnumbered those of the control group.Conclusion A subcutaneous tumor-suppressor mouse model for BCG for therapeutic use has been estab-lished.The anti-tumor effect may be generated by activating Th1-type immune response and increasing the level of cell secretion of IL-2 and IFN-γ,thus promoting cell-mediated immune response.
关键词
小鼠膀胱癌细胞/卡介苗/C57BL/6J小鼠/膀胱癌Key words
mouse bladder cancer cells/BCG/C57BL/6J mice/bladder cancer引用本文复制引用
出版年
2024