Zhao Zhu, Dai Juji, Yu Yan, Zhang Qian, Liu Sai, Huang Guanmeng, Zhang Zheng, Chen Tianke, Pan Rulu, Lu Liting, Zhang Wenyi, Liao Wanqin, Lu Xincheng
School of Basic Medical Sciences, Wenzhou Medical University, Wenzhou, China.
Front Oncol. 2019 Sep 11;9:864. doi: 10.3389/fonc.2019.00864. eCollection 2019.
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 . 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 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 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.
动物模型在抗癌治疗药物的研发中发挥着关键作用。以非侵入性方式快速评估局部原发性肝细胞癌（HCC）状态的能力将显著提高抗HCC治疗研究的有效性。然而，迄今为止，具有这一优势的动物模型极为稀少。在本研究中，我们开发了一种新型动物模型，用于快速评估针对原发性HCC的药物疗效。通过向具有免疫活性的肝癌发生报告基因（HCR）小鼠注射二乙基亚硝胺（DEN）诱导HCC，并通过组织病理学染色进行确认。利用生物发光成像（BLI）技术，以非侵入性方式纵向可视化并监测HCC的进展。两种临床药物的试验表明，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BLI强度检测准确评估了抗HCC药物的抑制作用。我们的研究成功建立了一种用于HCC治疗非侵入性实时监测的生物发光小鼠模型，这种HCR小鼠模型将成为潜在抗HCC药物筛选和新治疗策略开发的有用工具。
