前列腺癌抗原1蛋白表达下调对前列腺癌LNCaP细胞恶性生物学行为的影响  

Effect of downregulation of prostate cancer antigen-1 expression on malignant biological behavior of prostate cancer LNCaP cells

作　　者：刘秉乾[1] 王义昆[1] 武玉东[1] 魏金星[1] 李鑫[1] 

机构地区：[1]郑州大学第一附属医院泌尿外科,450052

出　　处：《中华肿瘤杂志》2013年第11期828-832,共5页Chinese Journal of Oncology

基　　金：基金项目：国家自然科学基金（30801151）

摘　　要：目的探讨前列腺癌抗原1（PCA-1）蛋白表达下调对前列腺癌LNCaP细胞增殖、细胞周期分布和细胞侵袭能力的影响，及其可能的分子机制。方法将PCA-1-siRNA和对照siRNA转染前列腺癌LNCaP细胞，采用四甲基偶氮唑蓝（MTT）法、流式细胞术和Transwell侵袭实验检测前列腺癌LNCaP细胞增殖、细胞周期分布和细胞侵袭能力，采用Western blot法检测前列腺癌LNCaP细胞中Bcl—xl、细胞周期素E（cyclin E）、基质金属蛋白酶9（MMP-9）和p21蛋白的表达水平。采用免疫组织化学法检测126例前列腺癌组织和88例良性前列腺增生（BPH）组织中PCA-1蛋白的表达情况。结果重组质粒PCA-1-siRNA可明显抑制前列腺癌LNCaP细胞中PCA-1蛋白的表达，转染48h后，未转染组、对照组和实验组LNCaP细胞中PCA-1蛋白的相对表达量分别为0．816±0．078、0．799±0．081和0．226±0．013。PCA-1蛋白表达下调能明显抑制前列腺癌LNCaP细胞增殖，将细胞周期阻滞在S期，并降低细胞的侵袭能力。PCA-1蛋白表达下调能明显降低LNCaP细胞中Bcl—xl、cyclinE和MMP-9的表达，同时提高p21的表达。PCA-1蛋白在前列腺癌组织和BPH组织中的阳性表达率分别为77．8％（98／126）和10．2％（9／88），差异有统计学意义（P〈0．05）。PCA-1蛋白表达与前列腺癌患者的Gleason评分、临床分期和骨转移情况有关（均P〈0．05）。结论PCA-1蛋白表达可能在前列腺癌的发展中具有重要作用，下调PCA-1表达可导致前列腺癌LNCaP细胞增殖、细胞周期分布和侵袭能力的改变，这可能与Bcl—xl、cyclinE、MMP-9和p21蛋白的表达变化相关。Objective To detect the expression of prostate cancer antigen-1 （ PCA-1 ） in prostate cancer, and to analyze the effects of downregulation of PCA-1 expression on malignant biological behavior of prostate cancer LNCaP cells, and to explore their possible molecular mechanisms. Methods PCA-1-siRNA and control siRNA were transfected into LNCaP cells with lipofectamine 2000. The cell cycle, proliferation and migration were determined by methyl thiazolyl tetrazolium （MTT） assay, flow eytometry and Transwell chambers, respectively. Western blotting was used to detect the expression of cyclin E, matrix metal｜opeptidase 9 （ MMP-9 ） and p21. Immunohistochetnistry was used to detect the expression of PCA-1 protein in 126 cases of prostate cancer and 88 cases of benign prostatic hyperplasia （BPH）. Results The positive rate of PCA-1 expression was 77.8% （ 98/126 ） in prostate cancer, and 10.2% （ 9/88 ） in BPH, and its expression was not significantly related to age, prostate specific antigen （PSA）, Eastern Cooperative Oneology Group （ECOG） score （ P 〉 0.05 ）, and was associated with Gleason score, TNM staging and bone metastasis （P 〈0.05）. Downregnlation of PCA-1 expression inhibited cell proliferation, arrested cell cycle at S phase and decreased cell migration of LNCaP cells. The downregulation of PCA-1 expression decreased the expression of Bcl-xl, cyclin E and MMP-9 proteins, but increased the expression of p21 proteins. Conclusions PCA-1 may play an important role in the development of prostate cancer. The downregnlation of PCA-1 expression can lead to changes in the proliferation, cell cycle and migration of prostate cancer LNCaP cells, and these effects may be associated with the decrease of Bcl-xl, cyclin E and MMP-9 proteinsand increase of p21 protein.

关 键 词：前列腺肿瘤 前列腺癌抗原1 LNCAP细胞 细胞增殖 细胞周期 

分 类 号：R737.25[医药卫生—肿瘤]