摘要
目的探讨脯氨酸羟化酶2(PHD2)蛋白在肝细胞癌(HCC)血管生成中的作用。方法 (1)采用免疫组织化学S-P法,检测72例肝细胞癌组织中的PHD2表达,结合肝细胞癌临床病理和MVD资料加以分析。(2)以不同浓度二氯化钴(CoCl2)诱导体外培养微血管内皮细胞(HMEC-1)缺氧。Western-blot方法检测PHD2、HIF-1α、VEGF蛋白表达水平,基质胶内皮细胞二维成管实验检测HMEC-1细胞的成管能力。结果 PHD2在72例HCC组织中的阳性表达率22.2%(16/72),低于在癌旁肝组织中阳性表达率68.1%(49/72)。HCC组织中PHD2高表达组MVD计数(52.1±4.3)显著性低于PHD2低表达组(69.2±5.5)。CoCl2处理后HMEC-1细胞PHD2蛋白表达下调,HIF-1α蛋白降解减少,VEGF表达上调,HMEC-1细胞成管能力下降,与对照组(正常肝组织)比较差异具有统计学意义(P<0.05)。结论缺氧微环境下,PHD2表达水平下调,内皮细胞增殖,但细胞成管能力下降,是导致HCC瘤体血管成熟度下降,促进HCC侵袭转移的重要影响因素之一。
Objective To explore the role of proline hydroxylase 2 （PHD2） in hepatocellular carcinoma angiogenesis.Methods （1）SP method immunohistochemical staining was used to detect PHD2 and microvessel density （MVD） was identified in 72 hepatocellular carcinoma tissues.Clinicopathological and microvessel density data were analysed.（2）Microvascular endothelial （HMEC-1） cell line was cultured in vitro,then,the cell lines were treated with different concentrations of cobalt chloride （treatment group）.The expression level of PHD2 protein was detected by Western blot.Tube formation capability of HMEC-1 cell in matrigel was examined.Results The expression positive rate of PHD2 in HCC tissues was significantly lower than that in peritumor liver tissues and normal liver tissue [22.2%（16/72）,68.1%（49/72）,84.6%（11/13）,respectively]（P0.05）.MVD in PHD2 higer expression group was lower than in PHD2 low expression （52.1±4.3 vs.69.2±5.5 respectively）（P0.05）.Compared with the control group （normal liver tissues）,the protein level of PHD2 and HIF-1α was decreased significantly,the protein level of VEGF was increased significantly,tube formation capability of HMEC-1 cell in matrigel were decreased after CoCl2 treatment （P0.05）.Conclusions In hypoxic microenvironment,the expression of PHD2 is decreased and endothelial cell proliferation is increased,but tube formation capability of endothelial cell is decreased,leading to decrease vascular maturity in HCC tumor which are the important factors to promote invasion and metastasis of HCC.
出处
《中国普通外科杂志》
CAS
CSCD
北大核心
2010年第10期1113-1117,共5页
China Journal of General Surgery
关键词
肝细胞癌
微环境
脯氨酸羟化酶2
血管生成
侵袭转移
Hepatocellular Carcinoma
Microenvironment
Proline Hydroxylase 2
Angiogenesis
Invasion Metastasis
