万珂增强NK细胞对前列腺癌细胞杀伤作用的实验研究  

Investigation of effect of Bortezomib on natural killer cell–mediated lysis of prostate cancer cells

作　　者：胡炜[1] 刘丹[1] 陈曲[1] 王嵬[1] Wei Hu;Dan Liu;Qu Chen;Wei Wang(Department of Medical Oncology,Jinzhou Central Hospital,Jinzhou,Liaoning 121001,China)

机构地区：[1]辽宁省锦州市中心医院肿瘤科,辽宁锦州121001

出　　处：《中国现代医学杂志》2018年第29期31-35,共5页China Journal of Modern Medicine

基　　金：辽宁省自然科学基金(No:201602269)

摘　　要：目的探讨万珂是否能够增强自然杀伤细胞(NK)对前列腺癌细胞的杀伤作用及其作用机制。方法以激素依赖性和激素非依赖性2种前列腺癌细胞株LNCaP和DU145为模型,不同浓度(0、10和20 nmol/L)万珂处理2种前列腺癌细胞株24 h。采用Annexin-V/PI法检测细胞凋亡率,流式细胞术检测人白细胞抗原-ABC(HLA-ABC)蛋白的表达,实时荧光定量聚合酶链反应检测HLA-C mRNA的表达。结果万珂能提高2种细胞系对NK细胞介导的杀伤作用的敏感性,而且在激素非依赖性前列腺细胞株DU145细胞中表现更明显。万珂能下调DU145细胞表面HLA-Ⅰ类分子水平。相对DU145细胞,万珂对激素依赖性前列腺癌LNCaP细胞不敏感,万珂处理后LNCaP细胞中HLA-Ⅰ类分子也没有改变。结论万珂通过下调HLA-Ⅰ类分子的表达,增强NK细胞对前列腺癌的杀伤能力,特别是增强对激素非依赖性前列腺细胞的杀伤,该作用能提高前列腺癌的治疗水平。Objective To investigate whether Bortezomib could sensitize NK cells to kill prostate cancer cells and its possible mechanism.Methods In this study,androgen-sensitive prostate cancer cell line LNCaP and androgen-insensitive human prostate cancer cell line DU145 were used as the objects of study,the prostate cancer cells were exposed to various concentrations(0,10 and 20 nmol/L)of Bortezomib for 24 h.Apoptosis was analyzed using Annexin-V/PI method.The expression of HLA-ABC protein was detected by flow cytometry.qRT-PCR was used to detect the expression of HLA-C mRNA.Results Bortezomib could increase the sensitivity of these two cell lines to NK cell-mediated killing,and DU145 cells were more sensitive to Bortezomib-induced apoptosis.Treatment with Bortezomib down-regulated the HLA-I molecule on the surface of DU145 cells;in contrast,LNCaP cells were not sensitized by this treatment,their HLA-I molecule did not change.Conclusions Bortezomib can enhance the anti-tumor ability of NK cells by down-regulation of the cell-surface expression of HLA-I,especially in androgeninsensitive human prostate cancer cells.This effect can be utilized to sensitize androgen-insensitive human prostate cancer to NK cell-mediated killing and improve current cancer therapies.

关 键 词：万珂 人类前列腺癌 自然杀伤细胞 人白细胞抗原-ABC 

分 类 号：R737.25[医药卫生—肿瘤]