Clinical Research Center, National Hospital Organization Nagasaki Medical Center, Department of Hepatology, Nagasaki University Graduate School of Biomedical Sciences, Omura, Japan.
J Surg Res. 2012 Jan;172(1):116-22. doi: 10.1016/j.jss.2010.07.057. Epub 2010 Sep 17.
A high incidence of recurrence after treatment is the most serious problem in hepatocellular carcinoma (HCC). Therefore, a new strategy for the treatment of the disease is needed. The aim of the present study was to investigate whether vitamin D binding protein-macrophage activating factor (DBP-maf) is able to inhibit the growth of HCC.
The effects of DBP-maf on endothelial cells and macrophage were evaluated by WST-1 assay and phagocytosis assay, respectively. Human HCC cells (HepG2) were implanted into the dorsum of severe combined immunodeficiency (SCID) mice. These mice were divided into control and DBP-maf treatment groups (n = 10/group). The mice in the treatment group received 40 ng/kg/d of DBP-maf for 21 d.
DBP-maf showed anti-proliferative activity against endothelial cells and also activated phagocytosis by macrophages. DBP-maf inhibited the growth of HCC cells (treatment group: 126 ± 18mm(3), untreated group: 1691.5 ± 546.9mm(3), P = 0.0077). Histologic examinations of the tumors revealed the microvessel density was reduced and more macrophage infiltration was demonstrated in the tumor of mice in the treatment group.
DBP-maf has at least two novel functions, namely, an anti-angiogenic activity and tumor killing activity through the activation of macrophages. DBP-maf may therefore represent a new strategy for the treatment of HCC.
治疗后复发率高是肝细胞癌（HCC）最严重的问题。因此，需要一种新的治疗策略。本研究旨在探讨维生素 D 结合蛋白-巨噬细胞激活因子（DBP-maf）是否能够抑制 HCC 的生长。
通过 WST-1 检测和吞噬试验分别评估了 DBP-maf 对内皮细胞和巨噬细胞的影响。将人 HCC 细胞（HepG2）植入严重联合免疫缺陷（SCID）小鼠的背部。将这些小鼠分为对照组和 DBP-maf 治疗组（n = 10/组）。治疗组小鼠接受 40 ng/kg/d 的 DBP-maf 治疗 21 天。
DBP-maf 对内皮细胞表现出抗增殖活性，并且还激活了巨噬细胞的吞噬作用。DBP-maf 抑制 HCC 细胞的生长（治疗组：126 ± 18mm3，未治疗组：1691.5 ± 546.9mm3，P = 0.0077）。肿瘤的组织学检查显示，治疗组小鼠肿瘤中的微血管密度降低，巨噬细胞浸润增多。
DBP-maf 具有至少两种新功能，即通过激活巨噬细胞具有抗血管生成活性和肿瘤杀伤活性。因此，DBP-maf 可能代表治疗 HCC 的一种新策略。
