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两种小鼠结直肠癌动物模型的特点比较与应用
Comparison of 2 different mouse models of colorectal cancer and their application
- 陆军军医大学学报 2024年46卷第2期 页码：91-99
- 作者机构：
1.610041 成都，电子科技大学附属肿瘤医院，放射肿瘤学四川省重点实验室，四川省肿瘤医院·研究所，四川省癌症防治中心，四川省肿瘤临床研究中心
2.610075 成都，成都中医药大学基础医学院
- 作者简介：
[刘登群，E-mail: dengqunliu@163.comLIU Dengqun, E-mail: dengqunliu@163.com
- 基金信息：四川省科技计划科技创新人才项目(2023JDRC0019);四川省中央引导地方科技发展专项(2022ZYD0091);四川省卫生健康委员会医学科技重点研发项目(21ZD008)
DOI：10.16016/j.2097-0927.202307077
中图分类号： R-332;R735.35;R735.37收稿：2023-07-16，
修回：2023-09-04，
纸质出版：2024-01-30
- 稿件说明：
移动端阅览
冯建华, 柳向军, 黄宇君, 等. 两种小鼠结直肠癌动物模型的特点比较与应用[J]. 陆军军医大学学报, 2024,46(2):91-99.
Jianhua FENG, Xiangjun LIU, Yujun HUANG, et al. Comparison of 2 different mouse models of colorectal cancer and their application[J]. Journal of Army Medical University, 2024, 46(2): 91-99.
冯建华, 柳向军, 黄宇君, 等. 两种小鼠结直肠癌动物模型的特点比较与应用[J]. 陆军军医大学学报, 2024,46(2):91-99. DOI： 10.16016/j.2097-0927.202307077.
Jianhua FENG, Xiangjun LIU, Yujun HUANG, et al. Comparison of 2 different mouse models of colorectal cancer and their application[J]. Journal of Army Medical University, 2024, 46(2): 91-99. DOI： 10.16016/j.2097-0927.202307077.
摘要
目的
2
建立炎症诱导和基因突变诱导结直肠癌小鼠模型并比较其特点。
方法
2
采用氧化偶氮甲烷(azoxymethane，AOM)联合葡聚糖硫酸钠(dextran sodium sulfate，DSS)建立炎症诱导结直肠癌小鼠模型，使用KPC小鼠建立携带Kras基因突变和Apc条件敲除的转基因结直肠癌小鼠模型。观察小鼠体质量、粪便性状和便血等大体状况，根据建模时间点取材小鼠结直肠标本并观察其成瘤情况。HE染色及Ki67免疫组化评估病理变化。使用tdTomato标记CDX2阳性上皮细胞。培养并比较两种结直肠癌类器官与正常结肠类器官的差异。
结果
2
AOM/DSS建模周期约50 d，其结直肠癌主要位于远段近肛门处和结肠中段；KPC模型形成结直肠癌约需8 d，肿瘤主要位于结肠近段。AOM/DSS模型中远段肿瘤部位组织结构紊乱，KPC模型中近段结肠黏膜层增厚且组织紊乱，存在大量未分化上皮细胞。AOM/DSS模型肿瘤组织内Ki67阳性细胞较癌旁组织中明显增多，KPC模型内近段结肠癌中存在大量Ki67阳性肿瘤细胞，远段结肠增殖水平正常。表达CDX2的tdTomato阳性上皮细胞主要位于结肠近段。两种模型均能培养得到增殖旺盛的肿瘤类器官。
结论
2
AOM/DSS结肠癌模型具有慢性炎症所致结直肠癌特点，适用于慢性炎症相关结直肠癌的研究；KPC模型产生肿瘤的肠段及细胞增殖活性可能与CDX2高表达密切相关，适合Kras基因突变结直肠癌研究，两种结直肠癌模型可互为补充。
Abstract
Objective
2
To establish and compare the characteristics of mouse models of colorectal cancer (CRC) induced by inflammation and gene mutation.
Methods
2
Inflammation-induced colorectal cancer mouse model was established using azoxymethane (AOM) combined with dextran sodium sulfate (DSS). The transgenic CRC mouse model carrying Kras gene mutation and Apc conditional knockout mutation was established by intraperitoneal injection of 100 mg/kg tamoxifen into KPC mice. The changes of body weight
fecal appearance and blood feces were observed during the modeling period. Colonic tissue samples were collected during the time points of CRC modeling
and then embedded and sectioned to observe tumor formation. HE and immunohistochemical staining of Ki67 were used to observe the pathological changes. Tandem dimer Tomato (tdTomato) was employed to determine the CDX2 expression in the colonic epithelial cells. CRC crypts were isolated and cultured to get tumor organoids
then compared with healthy colonic enteroids.
Results
2
It took about 50 d to establish AOM/DSS-induced CRC model
and the visible tumors were mainly observed at the distal colon close to the anus and at the middle section of colon. However
only about 8 d was needed for KPC mice to develop CRC
with the masses mostly locating in the proximal colon. In AOM/DSS model
disordered structure was observed in the distal tumor sites
and the KPC model had thickened and disrupted proximal mucosa and irregularly arranged tissues
with many undifferentiated epithelial cells. There were more Ki67
+
proliferative cells in the tumor tissues than the para-tumor tissues in AOM/DSS model
and larger amount of these cells were seen in the tumor in proximal section
but the distal colonic epithelium remained healthy proliferation.
In addition
tdTomato
+
CDX2-expressing colonic epithelia cells were observed mainly at the proximal colonic epithelium. Both AOM/DSS and KPC mice were capable to culture organoids of CRC.
Conclusion
2
AOM/DSS-induced CRC model presents the inflammatory process of CRC development
and it is suitable to the CRC study concerning chronic inflammation. The KPC CRC model is due to higher proliferative capacity of proximal colonic segment
in which CDX2 expressing higher than in the distal segment
so it is more convenient to Kras mutation related CRC study. These 2 CRC models can be alternatively adopted depending on different aims.
关键词
Keywords
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