Hepatocellular carcinoma (HCC) is widely known to be chemo-resistant and presents with significant liver disease resulting in low tolerability to systemic chemotherapy. As a counter measure, more targeted therapies such as trans-arterial chemoembolization (TACE) and trans-arterial radioembolization (TARE) have been developed. To further optimize these therapies, animal models are critical in elucidating the molecular events in disease progression and test new treatment options. The present study focuses on the development of a hepatoma bearing rat model. N1S1 rat hepatoma cells were transfected by a lentiviral method and injected into the liver of Sprague Dawley (SD) and Rowett Nude (RNU) rats. Longitudinal tumor growth was observed by bioluminescence imaging (BLI) and liver/tumor histology. In both models, tumors were visible within 4 days post cell inoculation. Tumor take rates were 52 % and 73 % for male and female SD rats, respectively, and 100 % for male RNU rats. By day 12 and 15 post inoculation, we recorded complete tumor regression in male and female SD rats. Liver histology showed advanced fibrosis in the tumor regressed SD rats, whilst RNU rats exhibited the characteristic sheet pattern of Novikoff tumor with mild liver fibrosis. Increased CD3 and TUNEL staining observed in SD rat livers may be key factors for tumor regression. Our data reveal that the immunocompetent SD rats are not recommended as a model for therapeutic investigations. The immunosuppressed RNU rats, however, are characterized by consistent and reliable tumor growth and thus a desirable model for future therapeutic investigations.

众所周知，肝细胞癌（HCC）具有化疗耐药性，并伴有严重的肝脏疾病，导致对全身化疗的耐受性较低。作为应对措施，已经开发了更有针对性的疗法，例如经动脉化疗栓塞（TACE）和经动脉放射栓塞（TARE）。为了进一步优化这些疗法，动物模型对于阐明疾病进展中的分子事件和测试新的治疗方案至关重要。本研究的重点是肝癌大鼠模型的开发。通过慢病毒方法转染N1S1大鼠肝癌细胞并注射到Sprague Dawley（SD）和Rowett Nude（RNU）大鼠的肝脏中。通过生物发光成像（BLI）和肝脏/肿瘤组织学观察肿瘤的纵向生长。在这两种模型中，细胞接种后 4 天内肿瘤就可见。雄性和雌性SD大鼠的肿瘤取出率分别为52%和73%，雄性RNU大鼠的肿瘤取出率为100%。到接种后第 12 天和第 15 天，我们记录了雄性和雌性 SD 大鼠的肿瘤完全消退。肝脏组织学显示肿瘤消退的SD大鼠出现晚期纤维化，而RNU大鼠则表现出Novikoff肿瘤的特征性片状模式并伴有轻度肝纤维化。在 SD 大鼠肝脏中观察到的 CD3 和 TUNEL 染色增加可能是肿瘤消退的关键因素。我们的数据表明，不推荐将免疫功能正常的 SD 大鼠作为治疗研究的模型。然而，免疫抑制的 RNU 大鼠的特点是肿瘤生长一致且可靠，因此是未来治疗研究的理想模型。