携带pGRIM-19-si-survivin共表达质粒的减毒沙门菌对前列腺癌移植瘤的体内抑制作用  

Attenuated Salmonella carrying pGRIM-19-si-survivin co-expression plasmid inhibits growth of prostate cancer subcutaneous xenografts in vivo

作　　者：赵晓晖[1] 芦丽莉[1] 葛贺[1] 李冰[1] 赵雪俭[2] 刘艳波[1] 

机构地区：[1]北华大学基础医学院病理生理学教研室,吉林吉林132013 [2]吉林大学前列腺疾病防治研究中心,吉林长春132001

出　　处：《中国病理生理杂志》2014年第6期961-967,共7页Chinese Journal of Pathophysiology

基　　金：国家自然科学基金青年项目(No.81302226);吉林省教育厅资助项目(No.20110146);吉林市科技局计划项目(No.201032235)

摘　　要：目的:探讨人减毒沙门菌携带pGRIM-19-si-survivin共表达质粒对人前列腺癌皮下移植瘤生长的抑制作用及相关机制。方法:复制裸鼠前列腺癌皮下移植瘤模型,通过腹腔注射携带共表达质粒的减毒沙门菌进行治疗,实时监测肿瘤体积;运用免疫组织化学染色法、RT-PCR法和TUNEL法检测携带pGRIM-19-si-survivin共表达质粒的减毒沙门菌对肿瘤抑制作用的相关机制。结果:与psi-survivin或pGRIM-19单基因治疗对照组比较,携带pGRIM-19-si-survivin共表达质粒减毒沙门菌组肿瘤体积明显缩小,其缩小率分别约为2.36和3.02倍;肿瘤组织内survivin mRNA及蛋白表达明显下降(P<0.05),GRIM-19 mRNA及蛋白表达明显增高(P<0.05),凋亡相关蛋白Bcl-xL、Stat3、cyclin D1和c-Myc的mRNA表达明显降低(P<0.05),血管内皮生长因子(VEGF)mRNA及Ki67蛋白表达降低而caspase-3 mRNA表达明显上调(P<0.05),同时细胞凋亡明显。结论:携带pGRIM-19-si-survivin共表达质粒的减毒沙门菌明显抑制裸鼠前列腺癌皮下移植瘤的生长,其发生机制与促进细胞凋亡及抑制肿瘤细胞增殖有关。AIM：To explore the effects of pGRIM-19-si-survivin co-expression plasmid carried by human attenuated Salmonella on prostate cancer subcutaneous xenograft growth in nude mice .METHODS： Prostate cancer xeno-graft model was established in nude mice .Co-expression plasmids carried by attenuated Salmonella were introduced by in-traperitoneal injection .The xenograft volumes were monitored timely .Immunohistochemical staining , RT-PCR and TUNEL assay were applied to investigate the related mechanisms that pGRIM-19-si-survivin inhibited tumor growth in vivo.RESULTS：Compared with psisurvivin and pGRIM-19 carried by attenuated Salmonella （ control groups ） , the tumor volumes were reduced markedly in pGRIM-19-si-survivin plasmid group .The mean shrinkage rates were 2.36 and 3.02 times. pGRIM-19-si-survivin coexpression plasmid carried by attenuated Salmonella inhibited survivin expression but strengthened GRIM-19 expression obviously （P〈0.05）.The mRNA expression of apoptosis-related proteins such as Bcl-xL, Stat3, cy-clin D1 and c-Myc was inhibited , and the vascular endothelial growth factor （ VEGF） mRNA and Ki67 protein were also in-hibited, but the caspase-3 mRNA expression was up-regulated （ P〈0.05 ） with significant cell apoptosis .CONCLUSION：pGRIM-19-si-survivin coexpression plasmid carried by human attenuated Salmonella inhibits the growth of prostate cancer subcutaneous xenografts in nude mice by promoting cell apoptosis and inhibiting prostatic cancer proliferation .

关 键 词：RNA干扰 存活蛋白 GRIM-19 前列腺肿瘤 减毒沙门菌 

分 类 号：R737.25[医药卫生—肿瘤]