胰凝乳蛋白酶样蛋白酶体的活性作为前列腺癌生物标志物的潜在应用

Potential application of chymotrypsin-like proteasome activity as a biomarker for prostate cancer

摘要:

目的 探讨胰凝乳蛋白酶样蛋白酶体（chymotrypsin-like proteasome，CLP）活性作为前列腺癌生物标志物的可行性。方法 检测在体和离体的蛋白酶体活性，同时检测核因子κB的抑制蛋白α（inhibitory protein α of nuclear factor κB，IκB-α）、Bcl-2相关X蛋白（BCL-2 associated X protein，Bax）和细胞周期蛋白依赖性激酶抑制因子（cyclin-dependent kinase inhibitor，p27）的表达。结果 与正常前列腺上皮细胞及对照小鼠前列腺组织相比，前列腺癌细胞和前列腺肿瘤异种移植物中蛋白酶体底物蛋白IκB-α、Bax和p27的表达水平降低，CLP的离体和在体活性分别升高70%和23%。结论 CLP的活性可能是一种潜在的前列腺癌生物标志物，可能适合前列腺特异性抗原（prostate-specific antigen，PSA）在前列腺癌诊断中的补充。

Abstract:

Objective To investigate the feasibility of chymotrypsin-like proteasome（CLP） activity as a biomarker for prostate cancer.Methods Proteasome activity was determined in vitro and in vivo. We also measured the expression of inhibitory protein α of nuclear factor κB（IκB-α），Bcl-2 associated X protein（Bax），and cyclin-dependent kinase inhibitor（p27）.Results CLP activity was elevated by 70% in vitro and 23% in vivo，and the expression levels of the proteasome substrate proteins IκB-α，Bax，and p27 decreased in prostate cancer cells and prostate tumor xenografts compared with normal prostate epithelial cells and control mouse prostate tissue.Conclusion CLP activity is a potential biomarker for prostate cancer and may be used to supplement prostate-specific antigen in clinical diagnosis of prostate cancer.