Non-invasive Bioluminescence Monitoring of Hepatocellular Carcinoma Therapy in an HCR Mouse Model
Non-invasive Bioluminescence Monitoring of Hepatocellular Carcinoma Therapy in an HCR Mouse Model
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DOI：
10.3389/fonc.2019.00864
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发表时间：
2019-09
影响因子：
4.7
通讯作者：
Zhu Zhao;Juji Dai;Yan Yu;Qian Zhang;Sai Liu;Guan‐li Huang;Zheng Zhang;Tianke Chen;Rulu Pan;Liting Lu;Wenyi Zhang;Wanqin Liao;Xincheng Lu
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文献类型：
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作者：
Zhu Zhao;Juji Dai;Yan Yu;Qian Zhang;Sai Liu;Guan‐li Huang;Zheng Zhang;Tianke Chen;Rulu Pan;Liting Lu;Wenyi Zhang;Wanqin Liao;Xincheng Lu
动物模型在抗癌疗法的发展中起着至关重要的作用。以非侵入性方式快速评估局部原发性肝细胞癌（HCC）状态的能力将显着提高抗HCC治疗研究的有效性。然而，迄今为止，具有这种优势的动物模型极为稀缺。在这项研究中，我们开发了一种新的动物模型，用于快速评估体内抗原发性肝癌的药物疗效。用二乙基亚硝胺（DEN）诱导免疫活性肝癌报告（HCR）小鼠肝癌，并通过组织病理学染色证实。使用生物发光成像（BLI）技术，以非侵入性方式纵向可视化和监测HCC进展。两种临床药物的测试显示，索拉非尼和奥沙利铂均以剂量依赖方式显著抑制小鼠肝脏中的BLI信号。BLI信号的体内强度与药物治疗后小鼠肝脏中的最终肿瘤负荷状态高度一致。通过体内BLI强度检测准确评价抗肝癌药物的抑制作用。我们的研究成功建立了一种用于无创实时监测HCC治疗的生物发光小鼠模型，该HCR小鼠模型将为潜在的抗HCC药物筛选和新的治疗策略开发提供有用的工具。
Animal models play crucial roles in the development of anticancer therapeutics. The ability to quickly assess the localized primary hepatocellular carcinoma (HCC) status in a non-invasive manner would significantly improve the effectiveness of anti-HCC therapeutic studies. However, to date, animal models with this advantage are extremely scarce. In this study, we developed a novel animal model for the fast assessment of drug efficacy against primary HCC in vivo. HCC was induced in immunocompetent hepatocarcinogenesis reporter (HCR) mice by diethylnitrosamine (DEN) injection and confirmed by histopathological staining. Using the bioluminescence imaging (BLI) technique, HCC progression was longitudinally visualized and monitored in a non-invasive way. Tests of two clinical drugs showed that both sorafenib and oxaliplatin significantly inhibited the BLI signal in mouse liver in a dose-dependent manner. The in vivo intensity of BLI signals was highly consistent with the final tumor burden status in mouse liver after drug treatment. The inhibitory effect of anti-HCC drugs was accurately evaluated through in vivo BLI intensity detection. Our study successfully established a bioluminescence mouse model for non-invasive real-time monitoring of HCC therapy, and this HCR mouse model would be a useful tool for potential anti-HCC drug screening and new therapeutic strategy development.