Establishment of image-guided radiotherapy of orthotopic hepatocellular carcinoma mouse model  

作　　者：Kaixiao Zhou Yabo Jiang Shuang Feng Wei Mo Jing Nie Jianping Cao Yang Jiao 

机构地区：[1]School of Radiation Medicine and Protection,State Key Laboratory of Radiation Medicine and Protection,Soochow University,Suzhou,China [2]The Six Department of Hepatic Surgery,Eastern Hepatobiliary Surgery Hospital,Navy Military Medical University,Shanghai,China [3]Department of Radiotherapy,Eastern Hepatobiliary Surgery Hospital,Navy Military Medical University,Shanghai,China

出　　处：《Animal Models and Experimental Medicine》2023年第5期419-426,共8页动物模型与实验医学（英文）

基　　金：Key R&D Program of China,Grant/Award Number:2022YFC2503700 and 2022YFC2503703;National Natural Science Foundation of China,Grant/Award Number:81773226,82103483 and U1967220;Shanghai Sailing Program,Grant/Award Number:20YF1459700。

摘　　要：Background:Hepatocellular carcinoma(HCC)is the most common type of liver cancer.Recently,developments in radiotherapy technology have led to radiotherapy becoming one of the main therapeutics of HCC.Therefore,a suitable animal model for radiotherapy of the orthotopic HCC mouse model is urgently needed.Methods:In the present study,Hepa1-6 cells were injected into the liver of C57BL/6 mice in situ to mimic the pathological characteristics of the original HCC.Tumor formation was monitored by applying magnetic resonance imaging techniques and verified by H&E histopathological staining,AFP staining,and Ki67 staining.A single dose of 10 Gy X-ray was applied to simulate clinical radiotherapy plans using image-guided radiotherapy(IGRT)equipment.The efficiency of radiotherapy was then assessed by examining tumor size and weight one week after radiation.Cleaved-caspase3 staining and TUNEL were used to assess apoptosis in tumor tissues.Results:Intrahepatic tumor development was detected in the liver according using MRI.A high-density shadow could be seen 10 days after cell injection,which indicated the formation of HCC in vivo.The tumors grew steadily bigger,and underwent precision radiotherapy 20 days after injection.The typical pathological characteristics of HCC,such as large,deeply stained nuclei and irregular cell size,were visible with H&E staining.After radiotherapy,significantly higher expression of the immunohistochemical markers Ki67 and AFP were detected in tumor tissue than in the nearby normal tissue.Compared with the control group,the tumor volume(p=0.05)and weight(p<0.05)of the irradiated group were significantly reduced.In addition,a higher frequency of apoptosis was identified in irradiated HCC tumor tissue using the TUNEL and cleaved-caspase3 staining assay.Conclusions:In a well-established orthotopic HCC model,MRI was utilized to monitor the formation of tumors,and IGRT was used to simulate clinical radiotherapy.The present study could provide a suitable preclinical system for HCC radiotherapyrelated stud

关 键 词：hepatocellular carcinoma orthotopic model RADIOTHERAPY 

分 类 号：R735.7[医药卫生—肿瘤] R-332[医药卫生—临床医学]