脑星形细胞瘤中HPA的表达及其对肿瘤细胞侵袭力的影响  

Expression of HPA in human astrocytoma and its effects on invasiveness of tumor cells

作　　者：刘宏雷[1] 易力[2] 翟晓莉[3] 

机构地区：[1]河北省石家庄市第三医院神经外科,050011 [2]河北医科大学第二医院病理科 [3]河北省石家庄市第三医院病理科,050011

出　　处：《河北医药》2016年第14期2130-2133,共4页Hebei Medical Journal

摘　　要：目的观察乙酰肝素酶（HPA）在人脑星形细胞瘤组织的表达及对肿瘤细胞侵袭力的影响。方法采用免疫组化Elivision TMplus两步法和Real time-PCR法检测75例星形细胞瘤组织和40例正常脑组织中HPA蛋白和mRNA表达情况。通过siRNA干扰技术沉默星形细胞瘤U87细胞中HPA表达,采用Real time PCR、Western blot、Transwell小室实验检测肿瘤细胞HPA、血管内皮生长因子（VEGF）、基质金属蛋白酶-9（MMP-9）表达及细胞侵袭力变化。结果正常脑组织未见HPA蛋白表达,星形细胞瘤组织中HPA阳性表达率为78.67%（59/75）,星形细胞瘤组织HPA阳性表达率显著高于正常脑组织,且其mRNA表达水平也显著高于正常脑组织,差异有统计学意义（P〈0.05）。星形细胞瘤Ⅱ~Ⅳ级组,HPA阳性表达率逐渐增加,差异有统计学意义（P〈0.05）;且有转移组HPA阳性表达率显著高于无转移组（P〈0.05）。siRNA能够有效抑制星形细胞瘤U87细胞中HPA表达,并下调VEGF、MMP-9表达,同时穿膜细胞数显著减少,差异有统计学意义（P〈0.05）。结论 HPA在星形细胞瘤组织异常高表达,随着肿瘤恶性程度增高而逐渐升高。siRNA沉默HPA后细胞侵袭力显著降低,HPA有可能成为治疗星形细胞瘤的潜在靶点。Objective To investigate the expression of heparanase（ HPA） in human astrocytoma and its effects on invasiveness of tumor cells. Methods The expression levels of HPA were detected by immunohistochemical assay and Real time- PCR in 75 cases of human astrocytoma tissues and 40 cases of normal brain tissues. The small interfering RNA（ siRNA） knockdown technique was used to silence the expressions of PHA protein and mRNA in astrocytoma U87 cells. The expression levels of HPA,vascular endothelium growth factor（ VEGF）,matrix metalloproteinases-9（ MMP） as well as the changes of invasiveness of tumor cells were detected by Real time-PCR,Western Blot and Transwell assay. Results The expressions of PHA were not observed in normal brain tissues. The positive expression rate of HPA protein was 78. 67%（ 59 /75） in astrocytoma tissues,which was significantly higher than that [0（ 0 /40） ] in normal brain tissues（ P 〈0. 05）,moreover,the positive expression rate of HPA mRNA was significantly higher than that in normal brain tissues（ P 〈0. 05）.The positive expression rate of HPA at gradeⅡ ~ Ⅳof astrocytoma was gradually increased,and the positive rate was 60. 00%（ 15 /25）,79. 31%（ 23 /29）,90. 48%（ 19 /21）,respectively,and there was a significant difference among them（ P 〈0. 05）. Furthermore the positive expression rate of HPA in tumor metastasis group was significantly higher than that in non-metastasis group（ P 〈0. 05）. The siRNA could effectively inhibit the expressions of HPA in U87 cells and could down-regulate the expressions of VEGF,MMP-9,at the same time,which could obviously decrease the cell counts of permeating cell membrane（ P 〈0. 05）. Conclusion The high-expressions of HPA exist in astrocytoma tissues,moreover,which are gradually increased with the malignant degree of tumor. The invasiveness of tumor cells is obviously decreased after HPA is silenced by siRNA,thus,PHA may become a potential target point in treatment of astrocytoma.

关 键 词：星形细胞瘤 乙酰肝素酶 侵袭 

分 类 号：R730.264.1[医药卫生—肿瘤]