桃叶珊瑚苷对前列腺癌的抑制作用及机制的体内外研究  

In vivo and in vitro study on the inhibitory effects and mechanism of aucubin on prostate cancer

作　　者：闫本纯 何春艳 李宏伟 南锡浩 张智慧 邸彦橙 田河 YAN Benchun;HE Chunyan;LI Hongwei;NAN Xihao;ZHANG Zhihui;DI Yancheng;TIAN He(Dept.of Urinary Surgery,Hongqi Hospital Affiliated to Mudanjiang Medical University,Heilongjiang Mudanjiang 157000,China;First Clinical Medical College,Mudanjiang Medical University,Heilongjiang Mudanjiang 157011,China)

机构地区：[1]牡丹江医学院附属红旗医院泌尿外科,黑龙江牡丹江157000 [2]牡丹江医学院第一临床医学院,黑龙江牡丹江157011

出　　处：《中国药房》2024年第13期1618-1623,共6页China Pharmacy

基　　金：黑龙江省省属高等学校基本科研业务费科研项目(No.2020-KYYWFMY-0030)。

摘　　要：目的 探讨桃叶珊瑚苷(AU)调节蛋白激酶B(Akt)/双微体同源基因2(MDM2)/p53信号通路对前列腺癌(PC)细胞增殖和肿瘤生长的影响。方法 将前列腺癌细胞PC3分为对照组、50μmol/L AU组、100μmol/L AU组、SC79(Akt激活剂)组(5μmol/L)、100μmol/L AU+SC79组,考察各组细胞的克隆能力和增殖能力,检测细胞凋亡率及细胞中Akt/MDM2/p53信号通路相关蛋白表达。建立异种移植肿瘤裸鼠模型,并将建模成功的裸鼠分为肿瘤组、AU组(80 mg/kg)、SC79组(50 mg/kg)和AU+SC79组(80mg/kg AU+50 mg/kg SC79),每组10只,每天给药1次,共21 d。末次给药后,称定肿瘤质量,检测肿瘤组织中细胞核相关抗原(Ki-67)及Akt/MDM2/p53信号通路相关蛋白表达。结果 细胞实验中,与对照组比较,50μmol/L AU组、100μmol/L AU组细胞克隆形成数、增殖率和Akt、MDM2蛋白的磷酸化水平均显著减少/降低(P<0.05),细胞凋亡率、p53蛋白表达水平均显著升高(P<0.05),但SC79组各指标变化趋势相反(P<0.05);100μmol/L AU+SC79组与100μmol/L AU组比较,克隆形成数、增殖率和Akt、MDM2蛋白的磷酸化水平均显著增加/升高(P<0.05),细胞凋亡率、p53蛋白表达水平均显著降低(P<0.05),但与SC79组比较各指标变化趋势相反(P<0.05)。体内实验中,与肿瘤组比较,AU组裸鼠的肿瘤质量及组织中Ki-67阳性表达和Akt、MDM2蛋白的磷酸化水平均显著降低(P<0.05),p53蛋白表达水平显著升高(P<0.05),但SC79组裸鼠的上述指标变化趋势相反(P<0.05);AU+SC79组与AU组比较,裸鼠的肿瘤质量及组织中Ki-67阳性表达和Akt、MDM2蛋白的磷酸化水平均显著升高(P<0.05),p53蛋白表达水平显著降低(P<0.05),但其与SC79组比较各指标变化趋势相反(P<0.05)。结论 AU可通过抑制Akt/MDM2/p53信号通路从而抑制PC细胞增殖及肿瘤生长。OBJECTIVE To investigate the effects of aucubin(AU)on the proliferation and tumor growth of prostate cancer(PC)cells by regulating the protein kinase B(Akt)/murine double minute2(MDM2)/p53 signaling pathway.METHODS Prostate cancer cell PC3 were separated into control group,50μmol/L AU group,100μmol/L AU group,SC79(Akt activator)group(5μmol/L),and 100μmol/L AU+SC79 group.The cell cloning and proliferation ability were investigated;the rate of cell apoptosis and the expressions of Akt/MDM2/p53 signaling pathway-related protein were detected.Meanwhile,xenograft tumor models of nude mice were constructed and separated into tumor group,AU group(80 mg/kg),SC79 group(50 mg/kg),and AU+SC79 group(80 mg/kg AU+50 mg/kg SC79),with 10 mice in each group.They were given relevant medicine,once a day,for 21 d.After the last medication,tumor weight was determined,and the expressions of nucleus-associated antigen(Ki-67)and Akt/MDM2/p53 signaling pathway-related protein were detected in tumor tissue.RESULTS In the cell experiment,compared with control group,the cell clonal formation number,proliferation rate and phosphorylation levels of Akt and MDM2 protein in 50μmol/L AU and 100μmol/L AU groups were significantly decreased(P<0.05),while the cell apoptosis rate and p53 protein expression levels were significantly increased(P<0.05);however,the change trend of each index in SC79 group was opposite(P<0.05).Compared with 100μmol/L AU group,the cell clonal formation number,proliferation rate and phosphorylation levels of Akt and MDM2 protein in 100μmol/L AU+SC79 group were significantly increased(P<0.05),while cell apoptosis rate and p53 protein expression levels were significantly decreased(P<0.05);however,compared with SC79 group,the changing trend of indexes was the opposite(P<0.05).In the in vivo experiment,compared with the tumor group,the tumor mass and Ki-67 positive expression and the phosphorylation levels of Akt and MDM2 protein in nude mice of AU group were significantly decreased(P<0.05),and the expression level of

关 键 词：桃叶珊瑚苷 Akt/MDM2/p53信号通路 前列腺癌 细胞增殖 肿瘤生长 

分 类 号：R965[医药卫生—药理学]