利多卡因调节Shh/Gli1信号通路对子宫内膜癌细胞活性和血管生成拟态的影响  

Effects of lidocaine on the activity and angiogenic mimicry of endometrial cancer cells byregulating the Shh/Gli1 signaling pathway

作　　者：王颖雪 王倩 宋永刚 WANG Yingxue;WANG Qian;SONG Yonggang(Department of Anesthesiology and Perioperative Medicine,Shandong Public Health Clinical Center,Jinan,Shandong 250000,China)

机构地区：[1]山东省公共卫生临床中心麻醉与围手术期医学科,山东济南250000

出　　处：《中国优生与遗传杂志》2024年第10期2026-2031,共6页Chinese Journal of Birth Health & Heredity

摘　　要：目的探讨利多卡因调节音猬因子(Shh)/胶质瘤相关癌基因同源物-1(Gli1)信号通路对子宫内膜癌(EC)细胞活性和血管生成拟态(VM)的影响。方法随机将HEC-1B细胞分为空白组、利多卡因低浓度(利多卡因-L,5 mmol/L)组、利多卡因中浓度(利多卡因-M,10 mmol/L)组、利多卡因高浓度(利多卡因-H,15 mmol/L)组、purmorphamine组、利多卡因-H+purmorphamine(1μmol/L)组,检测细胞增殖(平板克隆形成、MTT法)、凋亡(流式细胞术)、增殖(PCNA mRNA)、凋亡相关(Bcl-2、Bax mRNA)因子表达(qRT-PCR)、VM形成(3D模型)以及Shh/Gli1通路及VM形成相关(EphA2、VEGF)蛋白表达水平(Western blot检测)。结果与空白组相比,利多卡因-L组、利多卡因-M组、利多卡因-H组HEC-1B细胞凋亡率、Bax mRNA表达显著增加,克隆形成数、增殖率、VM形成管状结构数、PCNA、Bcl-2 mRNA、Shh、Gli1、EphA2、VEGF蛋白表达显著降低,呈剂量依赖性(P<0.05);与purmorphamine组相比,利多卡因-H+purmorphamine组HEC-1B细胞凋亡率、Bax mRNA表达显著增加,克隆形成数、增殖率、VM形成管状结构数、PCNA、Bcl-2 mRNA、Shh、Gli1、EphA2、VEGF蛋白表达显著降低(P<0.05);与利多卡因-H组相比,利多卡因-H+purmorphamine组HEC-1B细胞凋亡率、Bax mRNA表达显著降低,克隆形成数、增殖率、VM形成管状结构数、PCNA、Bcl-2 mRNA、Shh、Gli1、EphA2、VEGF蛋白表达显著增加(P<0.05)。结论利多卡因通过调节Shh/Gli1信号通路抑制EC细胞活性、VM形成。Objective To investigate the effects of lidocaine on the activity and vasculogenic mimicry(VM)of endometrial cancer(EC)cells by regulating the sonic hedgehog(Shh)/Glioma-associated hemolog-1(Gli1)signaling pathway.Methods HEC-1B cells were randomly separated into a blank group,a low concentration lidocaine(lidocaine-L,5 mmol/L)group,a medium concentration lidocaine(lidocaine-M,10 mmol/L)group,a high concentration lidocaine-H(15 mmol/L)group,a purporamine group,and a lidocaine-H+purporamine(1μmol/L)group,cell proliferation(plate clone formation,MTT assay),apoptosis(flow cytometry),proliferation(PCNA mRNA),apoptosis related(Bcl-2,Bax mRNA)factor expression(qRT-PCR),VM formation(3D model),as well as Shh/Gli1 pathway and VM formation related(EphA2,VEGF)protein expression levels(Western blot detection)were detected.Results Compared with the blank group,the apoptosis rate and Bax mRNA expression of HEC-1B cells in the lidocaine-L group,lidocaine-M group,and lidocaine-H group were obviously increased,the number of clones formed,proliferation rate,the number of VM formed tubular structures,the protein expression of PCNA,Bcl-2 mRNA,Shh,Gli1,EphA2,and VEGF were obviously reduced,in a dose-dependent manner(P<0.05).Compared with the purmorphamine group,the apoptosis rate and Bax mRNA expression of HEC-1B cells in the lidocaine-H+purmorphamine group were obviously increased,the number of clones formed,proliferation rate,the number of VM formed tubular structures,the protein expression of PCNA,Bcl-2 mRNA,Shh,Gli1,EphA2,and VEGF were obviously reduced(P<0.05).Compared with the lidocaine-H group,the apoptosis rate and Bax mRNA expression of HEC-1B cells in the lidocaine-H+purporamine group were obviously reduced,the number of clones formed,proliferation rate,the number of VM formed tubular structures,the protein expression of PCNA,Bcl-2 mRNA,Shh,Gli1,EphA2,and VEGF were obviously increased(P<0.05).Conclusion Lidocaine inhibits EC cell activity and VM formation by regulating the Shh/Gli1 signaling pathway.

关 键 词：利多卡因 Shh/Gli1信号通路 子宫内膜癌 血管生成拟态 

分 类 号：R737.33[医药卫生—肿瘤]