Establishment of a model of lung metastasis and recurrence of mice after bone marrow injection
Received:June 15, 2020  
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DOI:10. 3969 / j.issn.1005-4847. 2020. 05. 004
KeyWord:intraosseous injection; lung metastasis; postoperative tumor recurrence; animal model Conflicts of Interest: The authors declare no conflict of interest.
焦肖宁 上海中医药大学基础医学院,上海
侯怡飞 上海中医药大学基础医学院,上海
朱杨壮壮 上海中医药大学基础医学院,上海
苏琳 上海中医药大学基础医学院,上海
张飞 上海交通大学医学院附属新华医院,上海
陈晓 上海中医药大学基础医学院,上海
朱诗国 上海中医药大学基础医学院,上海
韦璐瑶 上海中医药大学基础医学院,上海
王万涛 上海中医药大学基础医学院,上海
王杰 上海中医药大学基础医学院,上海
朱娴丹 上海中医药大学科技实验中心,上海
邹纯朴 上海中医药大学基础医学院,上海
胥孜杭 上海中医药大学基础医学院,上海
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       Objective To establish a model of lung metastasis by bone marrow injection and a model of tumor recurrence after surgery to reveal the superiority and feasibility of the model of bone marrow injection to provide a new research basis for studying lung metastasis of malignant tumors. Methods The mice were divided into a mammary fat pad injection group, a subcutaneous injection group, a tail vein injection group, and a bone marrow injection group. Different models of 5 × 105 4T1 cells were injected via mammary fat pad injection, subcutaneous injection, tail vein injection, and bone marrow injection, and the growth, survival period, and lung metastasis efficiency of the primary tumors of model mice under different modeling method were observed. Different numbers of 4T1 cells were injected and the time of lung metastasis was observed. 4T1-luc cells were injected into the bone marrow to construct a postoperative tumor recurrence model. The mice were divided into a sham amputation group, a 3rd day amputation group, a 7th day amputation group, and a 10th day amputation group. Live imaging was performed every 7 days to observe lung metastasis in mice, while imaging was performed in the lungs of mice in the pseudo-amputation group and the 7th day amputation group to confirm the success of model construction. Results Compared with mammary fat pad injection and subcutaneous injection, bone marrow injection had no effect on the growth of the primary tumor, but the associated survival time was significantly shortened. Compared with mammary fat pad injection, subcutaneous injection, and tail vein injection, bone marrow injection had the highest lung metastasis efficiency. The bone marrow injection method required only 1 × 105 4T1 cells to cause lung metastasis on the 12th day. Mice with bone marrow injection still exhibited lung metastasis and recurrence of primary tumor after amputation. Conclusions A mouse model of lung metastasis can be successfully established by bone marrow injection along with a mouse model of tumor recurrence after surgery. The mouse model created using this injection method has the characteristics of a short survival time and high metastasis efficiency. It can be used to study the mechanism of lung metastasis of malignant tumors and the related screening of drugs for treating malignant tumors.
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