青藤碱调节CXCR4-STAT3轴对卵巢癌A2780细胞增殖、迁移和血管生成拟态的影响  

Effects of Sinomenine regulating CXCR4 - STAT3 axis on proliferation,migrationand angiogenic mimicry of ovarian cancer A2780 cells

作　　者：闫振宇[1] 郭锰[2] 杨然[3] 苏博[1] 张海燕[4] YAN Zhenyu;GUO Meng;YANG Ran;SU Bo;ZHANG Haiyan(Department of Pathology;Department of Oncology;Department of Gynaecology,Nanyang Central Hospital,Henan Nanyang 473000,China;Pathology Department,the First Affiliated Hospital of Nanyang Medical College,Henan Nanyang 473000,China)

机构地区：[1]南阳市中心医院病理科,河南南阳473000 [2]南阳市中心医院肿瘤科,河南南阳473000 [3]南阳市中心医院妇科,河南南阳473000 [4]南阳医学高等专科学校一附院病理科,河南南阳473000

出　　处：《现代肿瘤医学》2024年第16期2944-2951,共8页Journal of Modern Oncology

基　　金：河南省医学科技攻关联合共建项目(编号:LHGJ2019010435)。

摘　　要：目的:探讨青藤碱(Sinomenine)对卵巢癌细胞增殖、迁移和血管生成拟态的影响及作用机制。方法:使用不同浓度(0、0.25、0.50、1.0、2.0、4.0、8.0 mmol/L)的青藤碱分别处理A2780细胞24、48 h, CCK-8法检测细胞存活率。将A2780细胞随机分为对照(Control)组、CXCR4激活剂基质细胞衍生因子-1(SDF-1)(SDF-1,100 ng/mL)组、CXCR4抑制剂普乐沙福(Plerixafor, 500 ng/mL)组、青藤碱(Sinomenine, 1.0 mmol/L)组、Sinomenine+SDF-1(1.0 mmol/L Sinomenine+100 ng/mL SDF-1)组,分别检测A2780细胞增殖、迁移与侵袭,体外血管生成拟态形成实验检测青藤碱对血管生成拟态的影响,Western blot法检测血管内皮生长因子(VEGF)、上皮细胞激酶(EphA2)、基质金属蛋白酶9(MMP-9)、MMP-2、CXC趋化因子受体4(CXCR4)、信号转导与转录激活因子3(STAT3)、磷酸化STAT3(p-STAT3)蛋白表达。结果:青藤碱可有效抑制A2780细胞增殖,且呈浓度依赖性;青藤碱可显著抑制A2780细胞迁移、侵袭及血管生成拟态形成,并下调血管生成拟态标志蛋白VEGF、EphA2、MMP-9、MMP-2表达,抑制CXCR4、p-STAT3表达(P<0.05),青藤碱的这一抑制作用可被CXCR4激活剂减弱。结论:青藤碱可能通过抑制CXCR4-STAT3轴,抑制卵巢癌细胞增殖、迁移、侵袭及血管生成拟态形成。Objective:To investigate the influences and mechanism of Sinomenine on the proliferation,migration and angiogenesis mimicry of ovarian cancer cells.Methods:A2780 cells were treated with Sinomenine at different concentrations(0,0.25,0.50,1.0,2.0,4.0,8.0 mmol/L)for 24 and 48 h respectively,and the cell viability was detected by CCK-8 method.A2780 cells were randomly separated into Control group,CXCR4 activator stromal cell-derived factor-1(SDF-1)(SDF-1,100 ng/mL)group,CXCR4 inhibitor Plerixafor(Plerixafor,500 ng/mL)group,Sinomenine(1.0 mmol/L)group,and Sinomenine+SDF-1(1.0 mmol/L Sinomenine+100 ng/mL SDF-1)group.The proliferation,migration and invasion of A2780 cells were detected,respectively.The effect of Sinomenine on angiogenesis mimicry was detected by in vitro angiogenesis mimicry formation assay.Western blot was applied to detect the protein expression of vascular endothelial growth factor(VEGF),epithelial cell kinase(EphA2),matrix metalloproteinase 9(MMP-9),MMP-2,CXC chemokine receptor 4(CXCR4),signal transduction and transcriptional activator 3(STAT3),phosphorylated STAT3(p-STAT3).Results:Sinomenine could effectively inhibit the proliferation of A2780 cells in a concentration-dependent manner.Sinomenine could greatly inhibit the migration,invasion and angiogenesis mimicry formation of A2780 cells,down-regulate the expression of angiogenesis mimicry marker proteins VEGF,EphA2,MMP-9,MMP-2,and inhibit the expression of CXCR4 and p-STAT3(P<0.05),and this inhibitory effect of Sinomenine could be attenuated by CXCR4 activators.Conclusion:Sinomenine may inhibit proliferation,migration,invasion and angiogenic mimicry formation of ovarian cancer cells by inhibiting CXCR4-STAT3 axis.

关 键 词：青藤碱 CXC趋化因子受体4-信号转导与转录激活因子3轴 卵巢癌细胞 增殖 迁移 血管生成拟态 

分 类 号：R737.31[医药卫生—肿瘤]