荷IL-12新城疫病毒治疗结肠癌的实验及其机制探讨  

The experiment and mechanism study of Newcastle disease virus containing IL-12 in treating colon cancer

作　　者：王凤娇 韩继武[1] 王大秀 WANG Fengjiao;HAN Jiwu;WANG Daxiu(Department of Gastoenterology,the Fourth Affiliated Hospital of Harbin Medical University,Heilongjiang Harbin 150001,China)

机构地区：[1]哈尔滨医科大学附属第四医院消化内科,黑龙江哈尔滨150001

出　　处：《现代肿瘤医学》2021年第5期761-765,共5页Journal of Modern Oncology

摘　　要：目的:探讨荷IL-12新城疫病毒rClone30-IL-12瘤内注射治疗结肠癌的作用效果及可能机制。方法:RT-PCR法鉴定病毒中IL-12;构建荷CT26细胞的结肠癌模型,将荷瘤小鼠随机分为rClone30-IL-12组、奥沙利铂(OXA)组、磷酸盐缓冲液(PBS)组;给药后隔天记录瘤体直径(mm)、小鼠质量(g)和日常生活状态等;解剖脾脏、瘤体并记录瘤体质量(g);流式检测荷瘤小鼠脾脏NK细胞的表达情况。结果:病毒含IL-12基因;rClone30-IL-12组和OXA组荷瘤小鼠平均瘤体体积、瘤体质量相较于PBS组明显下降(P<0.01、P<0.01,P<0.01、P<0.05);OXA组荷瘤小鼠平均质量相较于rClone30-IL-12组和PBS组明显下降(P<0.01、P<0.01);rClone30-IL-12组荷瘤小鼠脾脏中NK细胞的比例显著高于PBS组和OXA组。结论:瘤内注射rClone30-IL-12可有效抑制结肠癌细胞的生长,其机制可能与新城疫病毒自身溶瘤作用及rClone30-IL-12释放活性IL-12刺激NK细胞的活化有关系;与化疗药物OXA相比,在相似临床效果的前提下, rClone30-IL-12的毒副反应更小。Objective:To investigate the effect and possible mechanism of rClone30-IL-12 in the treatment of colon cancer by intratumoral injection.Methods:Identifying IL-12 in viral rClone30-IL-12 by RT-PCR.Constructing the colon cancer model,the tumor-bearing mice were randomly divided into rClone30-IL-12 group,oxaliplatin(OXA) group and phosphate buffer solution(PBS) group.Recording the diameter of the tumor(mm),the weight of the mouse(g) and the state of daily life every other day after administration.Dissecte the spleen,tumor and recorde the tumor weight.Detect the expression of NK cells in spleen of tumor-bearing mice by flow cytometry.Results:rClone30-IL-12 virus contained IL-12 gene.The average tumor volume and tumor weight of the tumor-bearing mice in the rClone30-IL-12 group and the OXA group were significantly lower than those in the PBS group(P<0.01,P<0.01,P<0.01,P<0.05).The average body weight of tumor-bearing mice in the OXA group was significantly lower than that in the rClone30-IL-12 group and the PBS group(P<0.01,P<0.01).The proportion of NK cells in the spleen of rClone30-IL-12 group tumor-bearing mice was significantly higher than that of PBS group and OXA group.Conclusion:Intratumoral injection of rClone30-IL-12 can effectively inhibit the growth of colon cancer cells,and its mechanism may be related to the oncolytic effect of Newcastle disease virus and the activation of NK cells stimulated by rClone30-IL-12 release of IL-12.Compared with OXA,they has similar clinical effects,but rClone30-IL-12 has less toxic side effects.

关 键 词：重组新城疫病毒 结肠癌 白介素-12 NK细胞 

分 类 号：R735.3[医药卫生—肿瘤]