聚乙二醇化干扰素-α抑制人肝癌生长的实验研究

Peginterferon-αInhibits Tumor Growth in Nude Mice Bearing Human Hepatocellular Carcinoma Xenografts with High Metastatic Potential

目的：探讨聚乙二醇化干扰素-α抑制人肝癌高转移裸鼠模型LCI-D20肿瘤生长的作用。方法：将人肝癌高转移裸鼠模型LCI-D20随机分为对照组、小剂量常规干扰素-α组、大剂量常规干扰素-α组、小剂量聚乙二醇化干扰素-α组和大剂量聚乙二醇化干扰素-α组。用药4周后行血常规和肝肾功能检查,并观察裸鼠体重变化、肿瘤生长及肝内转移情况。结果：对照组、小剂量常规干扰素-α组、大剂量常规干扰素-α组肿瘤体积分别达到(3293±993)mm^3、(3134±869)mm^3和(2240±1048)mm^3,且发现肝内转移和腹壁浸润,而聚乙二醇化干扰素-α组无肿瘤存活,具有显著差异(P＜0.01)。2种剂量聚乙二醇化干扰素-α组白细胞计数均有下降(P=0.009和P=0.002)。结论：聚乙二醇化干扰素-α能抑制LCI-D20裸鼠模型中肝移植瘤的生长和肝内转移,其作用可能与血清中保持稳定的干扰素治疗浓度有关。

Objective：To investigate the therapeutic and side effects of Peginterferon-α on tumor growth in nude mice bearing human hepatocellular carcinoma xenografts with high metastatic potential. Methods： The nude mice bearing highly metastatic LCI-D20 tumor were randomly distributed into 5 groups and were administered with Interferon-α 2.5×10^7U·kg^-1·d^-1 tiw, Interferon-α 5×10^7U·kg^-1·d^-1 tiw, Peginterferon 15μg·d^-1 qw and Peginterferon-α 30μg·d^-1 qw for 28 consecutive days respectively. The weight of nude mice was measured once a week. The tumor size was calculated after the mice were killed. The blood was collected for the routine analysis and the examination of liver and renal function. Results： The tumor growth was not inhibited significantly in the Interferon-α 2.5 × 10^7 U·kg^-1·d^-1 tiw, Interferon -α5 × 10^7 U ·kg^-1·d^-1 tiw groups as compared with that of controls （P=0. 996, P=0. 287）. In the Peginterferon-α 15 μg·d^-1qw and Peginterferon-α 30μg·d^-1 qw groups, no tumor was found. The efficacy of Peginterferon-α was significantly higher than that of the common Interferon-α（P%O. 001）. Peginterferon-α showed no significant toxicity in terms of weight loss or liver and renal function damage. Conclusion： Peginterferom-α may inhibit the tumor growth in LCI-D20 nude mice.