维替泊芬抑制肾癌细胞769-P增殖及其机制  

Antitumor activity of Verteporfin in renal cell carcinoma 769-P cells and its mechanism

作　　者：刘国钦[1] 胡国强[2] 冼玉荣 曾贵林[1] 李姝君 LIU Guoqin;HU Guoqiang;XIAN Yurong;ZENG Guilin;LI Shujun(Department of Nephrology and Endocrinology,Xinhui District People＇s Hospital of Jiangmen city,Jiangmen 529100,China;Department ofNephrology,Jiangmen Central Hospital,Jiangmen 529100,China;First Department of Oncology,Affiliated Hospital of Guangdong MedicalUniversity,Zhanjiang 524000,China)

机构地区：[1]江门市新会区人民医院肾内内分泌科,广东江门529100 [2]江门市中心医院肾内科,广东江门529100 [3]广东医科大学附属医院肿瘤一区,广东湛江524000

出　　处：《分子影像学杂志》2018年第4期509-513,共5页Journal of Molecular Imaging

摘　　要：目的研究维替泊芬影响肾癌769-P细胞的作用及潜在机制。方法采用不同浓度(0、1、5、10μmol/L)维替泊芬处理肾癌细胞株769-P,分别采用CCK8检测维替泊芬对769-P细胞活性的抑制作用;流式细胞术分析维替泊芬促进769-P细胞凋亡及抑制细胞周期;划痕实验观察维替泊芬影响769-P细胞迁移能力;克隆形成实验观察维替泊芬抑制769-P细胞集落形成能力;荧光定量PCR法及免疫印迹法分别分析维替泊芬作用于769-P细胞后,CDK4、Bax、CyclinD1、Bcl-2、YAP、TEAD及caspase-3的表达量变化情况。结果维替泊芬对769-P细胞的半数抑制浓度为4.917μmol/L(P<0.05)。维替泊芬可诱导769-P细胞凋亡并阻滞细胞生长周期,抑制细胞增殖作用呈浓度及时间依赖性(P<0.05)。维替泊芬处理后769-P细胞迁移能力及克隆形成能力亦呈浓度依赖性降低(P<0.05)。维替泊芬处理后769-P细胞的转录和翻译水平均受影响,caspase-3被激活,Bax及CDK4表达量增加,YAP、Bcl-2、cyclinD1和TEAD表达量减少(P<0.05)。结论维替泊芬具有杀伤肾癌细胞的能力,为探寻肾癌新药开拓了新方向。Objective To explore the ability of Verteporfin killing renal cell carcinoma 769-P cells and its potential mechanism.Methods 769-P was treated with different concentrations （0, 1, 5 and 10 μmol/L） of Verteporfin. The effect of Verteporfin on769-P cell proliferation was assessed by CCK8. Flow cytometry was applied to examine the effect of Verteporfin on 769-P cellcycle and apoptosis. Wound healing assay and colony forming assay were applied to evaluate the capacity of cell migrationand colony formation, respectively. Quantitative Real-time PCR and Western blotting were applied to determine the mRNAand protein levels of CDK4, Bax, CyclinD1, Bcl-2, YAP, TEAD and caspase-3. Results Verteporfin significantly inhibited thegrowth of 769-P cells with an IC50 of 4.917 μM. Verteporfin induced both apoptosis and cell cycle arrest of 769-P cells in adose-dependent manner. The migration and colony forming ability were also inhibited by Verteporfin in a dose-dependentmanner. Verteporfin regulated both transcriptional and translational level in 769-P cells. CDK4 and Bax were up-regulatedwhile CyclinD1, Bcl-2, YAP and TEAD were down-regulated. Moreover, caspase-3 was activated. Conclusion Verteporfin hassignificant antitumor effect against renal tumor cells, suggesting it’s a novel therapeutic agent for renal cell carcinoma.

关 键 词：维替泊芬 肾癌 细胞周期 细胞凋亡 

分 类 号：R737.11[医药卫生—肿瘤]