Establishment of image‐guided radiotherapy of orthotopic hepatocellular carcinoma mouse model
Abstract 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 i...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2023-10-01
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| Series: | Animal Models and Experimental Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/ame2.12335 |
| _version_ | 1827779197282549760 |
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| author | Kaixiao Zhou Yabo Jiang Shuang Feng Wei Mo Jing Nie Jianping Cao Yang Jiao |
| author_facet | Kaixiao Zhou Yabo Jiang Shuang Feng Wei Mo Jing Nie Jianping Cao Yang Jiao |
| author_sort | Kaixiao Zhou |
| collection | DOAJ |
| description | Abstract 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 radiotherapy‐related studies. |
| first_indexed | 2024-03-11T14:47:10Z |
| format | Article |
| id | doaj.art-4ac356c3b760476185cfb8c5138926b1 |
| institution | Directory Open Access Journal |
| issn | 2576-2095 |
| language | English |
| last_indexed | 2024-03-11T14:47:10Z |
| publishDate | 2023-10-01 |
| publisher | Wiley |
| record_format | Article |
| series | Animal Models and Experimental Medicine |
| spelling | doaj.art-4ac356c3b760476185cfb8c5138926b12023-10-30T10:48:25ZengWileyAnimal Models and Experimental Medicine2576-20952023-10-016541942610.1002/ame2.12335Establishment of image‐guided radiotherapy of orthotopic hepatocellular carcinoma mouse modelKaixiao Zhou0Yabo Jiang1Shuang Feng2Wei Mo3Jing Nie4Jianping Cao5Yang Jiao6School of Radiation Medicine and Protection, State Key Laboratory of Radiation Medicine and Protection Soochow University Suzhou ChinaThe Six Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital Navy Military Medical University Shanghai ChinaDepartment of Radiotherapy Eastern Hepatobiliary Surgery Hospital, Navy Military Medical University Shanghai ChinaSchool of Radiation Medicine and Protection, State Key Laboratory of Radiation Medicine and Protection Soochow University Suzhou ChinaSchool of Radiation Medicine and Protection, State Key Laboratory of Radiation Medicine and Protection Soochow University Suzhou ChinaSchool of Radiation Medicine and Protection, State Key Laboratory of Radiation Medicine and Protection Soochow University Suzhou ChinaSchool of Radiation Medicine and Protection, State Key Laboratory of Radiation Medicine and Protection Soochow University Suzhou ChinaAbstract 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 radiotherapy‐related studies.https://doi.org/10.1002/ame2.12335hepatocellular carcinomaorthotopic modelradiotherapy |
| spellingShingle | Kaixiao Zhou Yabo Jiang Shuang Feng Wei Mo Jing Nie Jianping Cao Yang Jiao Establishment of image‐guided radiotherapy of orthotopic hepatocellular carcinoma mouse model Animal Models and Experimental Medicine hepatocellular carcinoma orthotopic model radiotherapy |
| title | Establishment of image‐guided radiotherapy of orthotopic hepatocellular carcinoma mouse model |
| title_full | Establishment of image‐guided radiotherapy of orthotopic hepatocellular carcinoma mouse model |
| title_fullStr | Establishment of image‐guided radiotherapy of orthotopic hepatocellular carcinoma mouse model |
| title_full_unstemmed | Establishment of image‐guided radiotherapy of orthotopic hepatocellular carcinoma mouse model |
| title_short | Establishment of image‐guided radiotherapy of orthotopic hepatocellular carcinoma mouse model |
| title_sort | establishment of image guided radiotherapy of orthotopic hepatocellular carcinoma mouse model |
| topic | hepatocellular carcinoma orthotopic model radiotherapy |
| url | https://doi.org/10.1002/ame2.12335 |
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