神经降压素在雄激素非依赖性前列腺肿瘤动物模型中的表达  

The Expression of Neurotensin in Animal Model of Androgen Independent Prostate Cancer

作　　者：王江 蒋宁 尚芝群 陈靖 方军凯 张超 牛远杰 

机构地区：[1]医科大学第二医院泌尿外科, 天津 300211 [2]医科大学第二医院泌尿外科 , 天津300211 [3]中国医学科学院生物医学工程研究所天津生物医学材料重点实验室

出　　处：《天津医药》2014年第9期878-882,共5页Tianjin Medical Journal

基　　金：国家重点基础研究发展计划973计划(2012CB518304);国家国际科技合作专项项目(2012DFG32220);天津市应用基础与前沿技术研究计划(14JCYBJC29800);天津市生物医学材料重点实验室开放课题(院所1309)

摘　　要：目的观察神经降压素(NT)在原位前列腺肿瘤动物模型中的表达。方法利用原位种植包埋法和外科手术去势技术对Balbc-nu裸鼠分别构建雄激素依赖、去势3 d和雄激素非依赖性原位前列腺肿瘤动物模型;Af-fymetrix基因芯片技术检测NT在3组肿瘤组织中mRNA的表达差异,运用荧光实时定量聚合酶链反应(qRT-PCR)验证结果;HE染色在光镜下观察肿瘤组织病理学改变;ELISA法测定裸鼠血清前列腺特异性抗原(PSA)浓度;免疫组织化学法检测3组肿瘤组织中NT的蛋白相对表达量。结果与雄激素依赖组比较,雄激素非依赖组和去势3 d组NTmRNA表达分别上调5.10和下调0.33;用RT-PCR和qRT-PCR验证其结果,雄激素非依赖组的表达水平较雄激素依赖组分别上调1.41和7.27(P<0.01),去势3 d组的表达水平分别下调0.78和0.46(P<0.05);肿瘤组织HE染色可见明显的核异型性和瘤节结构;雄激素依赖组PSA和NT结果均分别为(0.48±0.03)μg/L和0.031±0.008,去势3 d组均分别为(0.17±0.03)μg/L和0.021±0.004,雄激素非依赖组均分别为(0.87±0.02)μg/L和0.042±0.010;与雄激素依赖组比较,去势3 d组表达降低,雄激素非依赖组表达升高(P<0.01)。结论 NT在前列腺肿瘤由雄激素依赖向雄激素非依赖这一变化过程中起着一定的作用,可以作为雄激素非依赖性前列腺肿瘤治疗靶点和特异性诊断指标。Objective To study the different expressions of neurotensin （NT） at gene and protein level in orthotopic model of prostate cancer . Methods The animal models of androgen dependent prostate cancer（ADPC,castrated for 3 days） and androgen independent prostate cancer（AIPC） were established by planting tumor tissue or undergoing surgical castra-tion. Affymetrix microarray technology was carried out to compare the gene expressions of NT. The result was verified by qRT-PCR. HE staining was used to observe the change of pathology. ELSIA and immunohistochemistry technology were fi-nally performed to detect protein expression of prostate-specific antigen（PSA） and NT in three different groups of prostate cancer tumor tissues. Results The expression of NT was 5.10 times higher in AIPC group than that in ADPC group. The ex-pression of NT was 0.33 times lower in castrated 3-day group than that in ADPC group. Results of RT-PCR and qRT-PCR showed that the expression levels of NT gene were 1.41 and 7.27 times respectively higher in AIPC group than that in ADPC group,but the expression levels of NT gene were 0.78 and 0.46 times respectively lower in castrated 3-day group than that in ADPC group （P＆lt;0.05）. HE results showed that nuclear atypia and tumor structure in three groups. Immunohistochemistry and ELISA results showed that the values of PSA and NT were （0.48±0.03） and （0.031±0.008）μg/L in ADPC group;（0.17± 0.03） and （0.021±0.004）μg/L in castrated 3-day group,and （0.87±0.02） and （0.042±0.010）μg/L in AIPC group. There were significantly lower expressions of NT and PSA in castrated 3-day group that those of ADPC group （P＆lt;0.01）. Conclusion In the transition from ADPC to AIPC, the over-expression of NT suggested that NT may be associated with prostate cancer progression. NT may be used as a new therapeutic target and specific diagnostic method of AIPC.

关 键 词：前列腺肿瘤 小鼠 裸 疾病模型 动物 芯片分析技术 聚合酶链反应 免疫组织化学 神经降压肽 

分 类 号：R737.25[医药卫生—肿瘤] R349.6[医药卫生—临床医学]