五味子甲素对前列腺癌骨转移PC-3细胞增殖、迁移和侵袭的影响及作用机制研究  

Effect of deoxyschizandrin on proliferation,migration and invasion of PC-3 cells and its mechanism

作　　者：黄胜 龚蕊 刘赣赣 漆启华[1] 黄帅 HUANG Sheng;GONG Rui;LIU Gangan;QI Qihua;HUANG Shuai(Department of Orthopaedics,the First Affiliated Hospital ofNanchang University,Nanchang 330006,China;不详)

机构地区：[1]南昌大学第一附属医院骨科,南昌330006 [2]江西卫生职业学院临床医学系,南昌330052 [3]广州医科大学第二附属医院骨科,广州510260

出　　处：《实用医学杂志》2021年第7期851-857,共7页The Journal of Practical Medicine

基　　金：国家自然科学基金项目(编号:81702671);江西省自然科学基金项目(编号:20202BABL216047)。

摘　　要：目的探讨五味子甲素对前列腺癌骨转移PC-3细胞增殖、迁移、侵袭的影响及其潜在分子机制。方法 CCK-8法检测五味子甲素对PC-3细胞增殖的影响;Transwell检测五味子甲素对PC-3细胞迁移和侵袭的影响;q RT-PCR检测五味子甲素对miR-505-3p和TGF-β信号通路相关基因mRNA表达的影响;Western blot检测五味子甲素对TGF-β信号通路相关蛋白表达的影响。构建裸鼠移植瘤模型,肿瘤称重,免疫组织化学法检测SMAD2和SMAD3表达。结果五味子甲素作用PC-3细胞48 h时的IC50为15.74μmol/Lol/L,五味子甲素抑制PC-3细胞增殖、迁移和侵袭。五味子甲素上调PC-3细胞中miR-505-3p的表达,抑制SMAD2、SMAD3以及TGF-β信号传导的下游靶基因(包括IL-11、PTHRP、CTGF)的mRNA表达。下调miR-505-3p的表达可逆转五味子甲素对PC-3细胞增殖、迁移及侵袭的抑制作用。五味子甲素显著抑制移植瘤生长;五味子甲素上调肿瘤组织中miR-505-3p的表达,同时下调SMAD2和SMAD3蛋白的表达。结论五味子甲素抑制前列腺癌骨转移PC-3细胞的增殖、迁移及侵袭能力,其机制可能与五味子甲素上调miR-505-3p表达,靶向下调SMAD2和SMAD3,从而抑制TGF-β通路激活有关。Objective To investigate the effect of deoxyschizandrin on the proliferation,migration and invasion of prostate cancer bone metastasis PC-3 cells,and its potential molecular mechanism. Methods CCK-8 was used to detect the effect of deoxyschizandrin on proliferation of PC-3 cells. Transwell assay was used to detect the effect of deoxyschizandrin on migration and invasion of PC-3 cells. qRT-PCR was used to detect the effect of deoxyschizandrin on mRNA expression of miR-505-3p and TGF-β signaling pathway related genes. Western blot was used to detect the effect of deoxyschizandrin on expression of TGF-β signaling pathway related proteins. After the nude mouse xenograft model was constructed,the tumor was weighed,and miR-505-3p expression in tumor tissue was detected by q RT-PCR,and the expression of SMAD2 and SMAD3 was detected by immunohistochemistry.Results The IC50 of deoxyschiza on PC-3 cells for 48 h was 15.74 μmol/L. Deoxyschizandrin inhibited the proliferation,migration and invasion of PC-3 cells. Deoxyschizandrin upregulated miR-505-3p expression,and inhibited the mRNA expression of SMAD2,SMAD3,and downstream target genes of TGF-β signaling pathway(including IL-11,PTHRP and CTGF). Knockdown of miR-505-3p reversed the inhibitory effects of deoxyschizandrin on PC-3 cells proliferation,migration and invasion. Deoxyschizandrin significantly inhibited tumor growth in nude mouse xenograft model. Deoxyschizandrin upregulated miR-505-3p expression and repressed SMAD2 and SMAD3proteins expression in tumor tissues. Conclusion Deoxyschizandrin can upregulate miR-505-3p,which targets SMAD2 and SMAD3 to inhibit the proliferation,migration and invasion of PC-3 cells by way of suppressing the activation of TGF-β signaling pathway.

关 键 词：五味子甲素 前列腺癌 miR-505-3p TGF-Β信号通路 

分 类 号：R285.5[医药卫生—中药学]