基于microcarrier 6正常免疫鼠人源宫颈癌移植瘤模型的构建及其临床应用意义  

Construction of a human cervical cancer xenograft model in normal immunized mice based on microcarrier 6and its clinical significance

作　　者：刘昆燕 张秋实[2] 张凯[3] 洪丰[4] 王全义[5] 彭一晴 赵影 段亚楠 周润生 彭存旭[7] LIU Kun-yan;ZHANG Qiu-shi;ZHANG Kai(Medical College Jining University,Jining 272000,China)

机构地区：[1]济宁医学院临床医学院,山东济宁272000 [2]广东省第二人民医院妇科(妇幼健康研究所) [3]吉林大学第二医院 [4]济宁医学院附属医院中美肝病与免疫研究所 [5]济宁医学院附属医院病理科 [6]济宁医学院附属医院生殖医学科 [7]济宁医学院附属医院妇科

出　　处：《中国实验诊断学》2022年第4期572-577,共6页Chinese Journal of Laboratory Diagnosis

基　　金：国家自然科学基金(81170395、81570556)。

摘　　要：目的 基于新型3D微载体(microcarrier 6),复合人原代宫颈癌细胞,皮下接种于具有正常免疫功能的小鼠,以期建立新型宫颈癌人源肿瘤移植瘤动物模型(PDX),并分析正常免疫鼠移植瘤病理学特点。方法 将75只雌性C57BL/6小鼠按移植物不同随机分为三组:细胞对照组、空白对照组和实验组。从新鲜手术标本宫颈癌组织中分离提取原代宫颈癌细胞,并与microcarrier 6共孵育,在体外构建3D微肿瘤模型。将构建的宫颈癌细胞-微载体植入小鼠皮下构建正常免疫小鼠患者来源的宫颈癌移植瘤模型。观察成瘤时间、成瘤率;观察对比肿瘤患者与其对应的移植瘤病理HE染色及应用免疫组化检测P16、CK5/6在各组移植瘤中的表达情况。结果 细胞对照组均没有小鼠成瘤,实验组5次实验,总成瘤率高达88%,成瘤时间10天左右,移植瘤生长速度快,HE染色和免疫组化均符合人宫颈癌特点。结论 本实验基于microcarrier 6复合患者来源的原代宫颈癌细胞在正常免疫小鼠体内成功建立了新型人宫颈癌PDX模型,该模型能更好地揭示宫颈癌的发生发展及转归与机体免疫之间的内在关系,更好地研究宫颈癌在机体中发生、发展机制,为免疫治疗提供了新的更有价值的动物模型。Objective Based on a novel 3D microcarrier(microcarrier 6),compound human primary cervical cancer cells subcutaneously inoculated into mice with normal immune function,in order to establish a new type of cervical cancer human tumor xenograft animal model(patient-derived xenografts,PDX),and analyzed the pathological characteristics of transplanted tumors in normal immunized mice.Methods 75 female C57 BL/6 mice were randomly divided into three groups according to different grafts:cell control group,blank control group and experimental group.Primary cervical cancer cells were isolated and extracted from fresh surgical specimens of cervical cancer tissue,and incubated with microcarrier 6 to construct a 3D tumor culture model in vitro.The constructed cervical cancer cells-microcarriers were implanted into mice subcutaneously to construct a patient-derived cervical cancer xenograft model in normal immune mice.Observe the tumor formation time and tumor formation rate.The pathological HE staining of tumor patients and their corresponding xenografts,and the expression of P16 and CK5/6 in xenografts of each group were detected by immunohistochemistry.Results There was no tumor formation in the control group.The total tumor formation rate was as high as 88%in the experimental group after 5 experiments.The tumor formation time was about 10 days.The transplanted tumor grew rapidly.Conclusion In this experiment,a novel human cervical cancer PDX model was successfully established in normal immunized mice based on the microcarrier 6 compound patient-derived primary cervical cancer cells.The internal relationship between them,better research on the occurrence and development mechanism of cervical cancer in the body,especially immunotherapy,provide new and more valuable animal models.

关 键 词：子宫颈肿瘤 原代肿瘤 MICROCARRIER 免疫 异种移植 动物模型 

分 类 号：R737.33[医药卫生—肿瘤]