Vitamin D Binding Protein-Macrophage Activating Factor Inhibits HCC in SCID Mice
Vitamin D Binding Protein-Macrophage Activating Factor Inhibits HCC in SCID Mice
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DOI：
10.1016/j.jss.2010.07.057
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发表时间：
2012-01-01
影响因子：
2.2
通讯作者：
Fujioka, Hikaru
中科院分区：
文献类型：
--
作者：
Nonaka, Koichi;Onizuka, Shinya;Fujioka, Hikaru
背景治疗后复发率高是肝细胞癌（HCC）最严重的问题。因此，需要一种治疗该疾病的新策略。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）是否具有抑制肝癌生长的作用。采用WST-1法和吞噬实验观察DBP-maf对内皮细胞和巨噬细胞的作用。将人肝癌细胞（HepG 2）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处理组（n = 10只/组）。治疗组小鼠每日灌胃40 ng/kg的DBP-maf，连续21 d。DBP-maf对内皮细胞显示出抗增殖活性，并且还激活巨噬细胞的吞噬作用。DBP-maf抑制肝癌细胞生长（治疗组：126 ± 18 mm（3），未治疗组：1691.5 ± 546.9mm（3），P = 0.0077）。肿瘤组织学检查显示治疗组小鼠肿瘤微血管密度降低，巨噬细胞浸润增多。DBP-maf具有至少两种新的功能，即抗血管生成活性和通过激活巨噬细胞的肿瘤杀伤活性。因此，DBP-maf可能代表一种治疗HCC的新策略。(C)2012 Elsevier Inc. All rights reserved.
Background. 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.Methods. 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.Results. 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.Conclusion. 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. (C) 2012 Elsevier Inc. All rights reserved.