布托啡诺调节Wnt/β-catenin信号通路对肺癌细胞增殖迁移和血管生成的影响  

Effects of Butorphanol on Proliferation Migration and Angiogenesis of Lung Cancer Cells by Regulating the Wnt/β-Catenin Signaling Pathway

作　　者：文竹[1] 陈婷婷[2] WEN Zhu(Mianyang Central Hospital,Sichuan Mianyang 621000,China)

机构地区：[1]四川省绵阳市中心医院麻醉科,四川绵阳621000 [2]四川省眉山市人民医院麻醉科,四川眉山620000

出　　处：《河北医学》2024年第5期705-710,共6页Hebei Medicine

基　　金：四川省眉山市人民医院科研项目,(编号:KJZD202119)。

摘　　要：目的:探讨布托啡诺调节Wnt/β-catenin信号通路对肺癌细胞增殖、迁移和血管生成的影响。方法:将肺癌H1299细胞分为对照组、布托啡诺低、高剂量组、布托啡诺高剂量+LiCl(Wnt/β-catenin信号通路激活剂)组、FH535组(Wnt/β-catenin信号通路抑制剂)。克隆形成实验检测细胞克隆能力;Transwell实验检测细胞迁移和侵袭;流式细胞术检测细胞凋亡率;血管拟态形成实验观察血管生成情况;western blot检测VEGF-A、VE-cadherin、Bcl-2、Bax、MMP-9、β-catenin、c-Myc和cyclin D1蛋白表达。结果:对照组H1299细胞管腔结构完整;与对照组相比,布托啡诺低、高剂量组和FH535组H1299细胞克隆形成率、细胞迁移和侵袭个数、管腔数量及VEGF-A、VE-cadherin、Bcl-2、MMP-9、β-catenin、c-Myc和cyclin D1蛋白表达降低,细胞凋亡率和Bax蛋白表达升高(P<0.05);LiCl可部分逆转布托啡诺对H1299细胞恶性生物学行为的抑制(P<0.05);FH535组H1299细胞各项检测指标与布托啡诺高剂量组处于同一水平(P<0.05)。结论:布托啡诺能够诱导肺癌细胞凋亡,阻滞迁移、增殖和血管生长,进而阻止肺癌的发生发展,其机制与阻断Wnt/β-catenin信号通路激活相关。Objective:To investigate the effects of buprenorphine on the proliferation,migration,and angiogenesis of lung cancer cells by regulating the Wnt/β-catenin signaling pathway.Methods:Human lung cancer H1299 cells were divided into the control group,low-dose and high-dose buprenorphine groups,high-dose buprenorphine+LiCl(Wnt/β-catenin signaling pathway activator)group,and FH535 group(Wnt/β-catenin signaling pathway inhibitor).The colony formation assay was used to detect the colony formation ability of cells;the Transwell assay was used to detect cell migration and invasion;flow cytometry was used to detect the cell apoptosis rate;the vascular mimicry formation assay was used to observe the angiogenesis;and Western blot was used to detect the expression of VEGF-A,VE-cadherin,Bcl-2,Bax,MMP-9,β-catenin,c-Myc,and cyclin D1 proteins.Results:The lumen structure of H1299 cells in the control group was intact;compared with the control group,the clone formation rate of H1299 cells,the numbers of cell migration and invasion,number of lumens,and the expression of VEGF-A,VE cadherin,Bcl-2,MMP-9,β-catenin,c-Myc,and cyclin D1 proteins were greatly reduced in the low-dose butorphanol group,high-dose butorphanol group,and FH535 group,the apoptosis rate and the expression of Bax protein were greatly increased(P<0.05);LiCl was able to partially reverse the inhibitory effect of butorphanol on the malignant biological behavior of H1299 cells(P<0.05);the various detection indicators of H1299 cells in the FH535 group were at the same level as those in the high-dose Butorphanol group(P<0.05).Conclusion:Butorphanol can induce apoptosis of lung cancer cells,block migration,proliferation and vascular growth,and then prevent the occurrence and development of lung cancer.The mechanism is related to blocking the activation of Wnt/β-catenin signaling pathway.

关 键 词：肺癌 布托啡诺 WNT/Β-CATENIN信号通路 血管生成 

分 类 号：R96[医药卫生—药理学]