Pim-1与裸鼠前列腺肿瘤内分泌治疗相关性的研究  

Correlation between the expression of Pim-1 and androgen-deprivation therapy for prostate cancer

作　　者：王江[1,2] 权昌益[1] 常文亮[1] 尚芝群[1] 蒋宁[1] 李博[1] 牛远杰[1] 

机构地区：[1]天津医科大学第二医院泌尿外科天津市泌尿外科研究所,天津300211 [2]天津市计划生育研究所男性泌尿科,天津300131

出　　处：《中华男科学杂志》2015年第9期775-781,共7页National Journal of Andrology

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)~~

摘　　要：目的:利用外科手术去势模拟内分泌治疗,研究Pim-1基因在LNCa P原位前列腺肿瘤裸鼠模型上的表达。方法:利用LNCa P细胞在BALBc裸鼠分别建立雄激素依赖、内分泌治疗和去势抵抗性前列腺肿瘤原位动物模型,采用RT-PCR、qRT-PCR、ELISA和免疫组化等技术检测Pim-1、前列腺特异性抗原(PSA)和雄激素受体(AR)在3组肿瘤组织中的表达差异。结果:RT-PCR结果:电泳结果显示雄激素依赖组与去势抵抗组的相对灰度比值分别为0.59±0.01和1.14±0.02,与内分泌治疗组0.62±0.03比较差异均具有统计学意义(P<0.05);qRT-PCR结果:雄激素依赖组与去势抵抗组的Pim-1△Ct值均分别为6.15±0.34和4.56±0.23,与内分泌治疗组5.11±0.21比较差异均具有统计学意义(P<0.05);应用2-△△Ct相对定量方法分析数据,内分泌治疗组和去势抵抗组Pim-1的扩增产物均较雄激素依赖组分别上调2.05倍和3.01倍;ELSIA结果:空白对照组裸鼠PSA浓度为0μg/L,雄激素依赖组和去势抵抗组均分别为(480±25)、(870±23)pg/ml,与内分泌治疗组(170±32)pg/ml比较差异有统计学意义(P<0.01);免疫组化结果:雄激素依赖组Pim-1和AR的平均光密度比值分别为0.017±0.002和0.032±0.009,去势抵抗组分别为0.024±0.002和0.040±0.011,内分泌治疗组均分别为0.018±0.001和0.019±0.006;雄激素依赖组和去势抵抗组的Pim-1及AR的平均光密度比值均与内分泌治疗组差异有统计学意义(P<0.01)。结论:Pim-1在祼鼠前列腺肿瘤内分泌治疗期呈现出高表达状态,对前列腺肿瘤的发展和转移起很大作用。Objective ： To investigate the expression of the Pim-1 gene in the LNCaP cells of the animal model of orthotopically implanted prostate cancer by surgical castration simulating androgen-deprivation therapy. Methods： We equally allocated 32 male BALBc-nu mice into 4 groups, androgen-dependent prostate cancer （ADPC）, androgen-deprivation therapy （ADT） , castration-resistant prostate cancer （CRPC） and blank control, and established the models of orthotopically implanted tumor using human prostate cancer LNCaP cells. We detected and compared the expressions of Pim-1, PSA, and androgen receptor （AR） in the tumor tissues of different groups by RT-PCR, qRT-PCR, ELSIA and immunohistochemistry. Results： The relative gray scales in the ADPC and CRPC groups were 0.59 ± 0.01 and 1.14 ± 0.02, with statistically significant differences from 0.62 ± 0.03 in the ADT group （ P 〈 0.05） , and the △Ct values of Pim-1 were 6.15 ± 0.34 and 4.56 ± 0.23 in the former two groups, also with significant differences from 5.11±0.21 in the latter （P 〈 0.05 ）. The results of 2-△△ct relative quantification analysis showed that the amplification products of Pim-1 in the ADT and CRPC groups increased 2.05 and 3.01 times respectively that of the ADPC group. The concentration of PSA was significantly higher in the ADPC （ [480 ±25] pg/ml） and CRPC （ [870±23] pg/ml） than in the ADT （ [170±32] pg/ml） and blank control groups （0 μg/L） （P 〈0.01 ）. The mean optical densities of Pim-1 and AR proteins were 0. 017 ±0.032 and 0. 032 ±0.009 in the ADPC group and 0. 024±0. 002 and 0. 040± 0. 011 in the CRPC group, both with significant differences from those in the ADT group （0.018 ±0.001 and 0. 019 ± 0. 006） （P 〈 0. 01 ）. Conclusion： Pim-1 is highly expressed in nude mice with prostate cancer receiving androgen-deprivation therapy and plays an important role in the progression and metastasis of prostate cancer.

关 键 词：雄激素依赖性前列腺肿瘤 内分泌治疗 去势抵抗性前列腺肿瘤 PIM-1 裸鼠 原位种植 

分 类 号：R737.25[医药卫生—肿瘤]