实用医学杂志 ›› 2023, Vol. 39 ›› Issue (11): 1403-1408.doi: 10.3969/j.issn.1006⁃5725.2023.11.014

• 基础研究 • 上一篇    下一篇

利多卡因通过SHH/GLI 信号通路对胶质瘤 细胞恶性生物学行为的影响 

马俊 向梅    

  1. 武汉市武昌医院麻醉科(武汉 430063) 
  • 出版日期:2023-06-10 发布日期:2023-06-10
  • 通讯作者: 向梅 E⁃mail:searaez@21cn.com
  • 基金资助:
    湖北省自然科学基金项目(编号:2017FFB6301) 

Effects of lidocaine on the malignant biological behavior of glioma cells through SHH/GLI signaling pathway 

MA Jun,XIANG Mei.    

  1. Department of Anesthesiology,Wuhan Wuchang Hospital,Wuhan 430063,China 
  • Online:2023-06-10 Published:2023-06-10
  • Contact: XIANG Mei E⁃mail:searaez@21cn.com

摘要:

目的 探讨利多卡因(Lid)调节 SHH/GLI 信号通路对胶质瘤细胞恶性生物学行为的影响。 方法 将 U87 细胞分为 U87 组、L⁃Lid 组、M⁃Lid 组、H⁃Lid 组、PM 组、H⁃Lid + PM 组。U87 组未做任何处理,L⁃Lid组、M⁃Lid组、H⁃Lid组分别用5、10、15 mmol/L Lid处理U87细胞,PM组用1 μmol/L的SHH/GLI信号 通路激活剂 PM 处理 U87 细胞,H⁃Lid + PM 组用 15 mmol/L Lid 和 1 μmol/L 的 PM 共同处理 U87 细胞。CCK8 检测 U87 细胞增殖;流式细胞术检测 U87 细胞凋亡;Transwell 检测 U87 细胞迁移、侵袭能力;Western blot 检 测 SHH/GLI 蛋白、凋亡蛋白表达;荷瘤小鼠模型验证 Lid 对 U87 细胞移植瘤的影响。结果 与 U87 组相 比,L⁃Lid 组、M⁃Lid 组、H⁃Lid 组的 OD 值、U87 细胞迁移、侵袭数量、Bcl⁃2、SHH、GLI3 蛋白水平、小鼠肿瘤体 积依次显著下降(P < 0.05),凋亡率、Bax 蛋白水平依次显著升高(P < 0.05);而 PM 组 OD 值、U87 细胞迁 移、侵袭数量、Bcl⁃2、SHH、GLI3 蛋白水平、小鼠肿瘤体积显著升高(P < 0.05),凋亡率、Bax 蛋白水平显著 下降(P < 0.05);PM 消除了 H⁃Lid 对 U87 细胞恶性生物学行为的抑制作用。Lid 处理后移植瘤小鼠存活数 量增加,而 PM 处理后移植瘤小鼠存活数量减少,H⁃Lid + PM 组与 L⁃Lid 组数量相同。结论 Lid 可能通过下调SHH/GLI 信号通路抑制U87细胞增殖,促进细胞凋亡,进而抑制胶质瘤的进展。 

关键词: 利多卡因, SHH/GLI 信号通路, 胶质瘤, 增殖, 凋亡

Abstract:

Objective To investigate the impact of lidocaine(Lid)on malignant biological behavior of glioma cells by regulating SHH/GLI signal pathway. Methods The U87 cells were divided into U87 group,L⁃Lid group,M⁃Lid group,H⁃Lid group,PM group,and H⁃Lid + PM group. No treatment was performed on U87 cells in L⁃Lid group,M⁃Lid group,and H⁃Lid group. U87 cells were treated with 5,10,and 15 mmol/L Lid,respectively, while PM group was treated with 1 mmol/L Lid μ U87 cells were treated with mol/L of SHH/GLI signal pathway activator PM,while H⁃Lid + PM group was treated with 15 mmol/L Lid and 1 μ The U87 cells were co treated with mol/L of PM. CCK8 was applied to detect U87 cell proliferation;flow cytometry was applied to detect U87 cell apoptosis;Transwell was applied to detect the migration and invasion abilities of U87 cells;Western blot was applied to detect the expression of SHH/GLI protein and apoptosis protein;the tumor⁃bearing mouse model was applied to verify the effect of Lid on U87 cell transplanted tumor. Results Compared with U87 group,the OD value,num⁃ bers of U87 cell migration and invasion,the protein levels of Bcl⁃2,SHH and GLI3,and tumor volume of mice in L⁃Lid group,M⁃Lid group and H⁃Lid group decreased obviously in turn(P < 0.05),the apoptosis rate and Bax protein level increased obviously in turn(P < 0.05);the OD value,numbers of U87 cell migration and invasion,the protein levels of Bcl⁃2,SHH and GLI3,and tumor volume of mice in PM group were obviously increased(P < 0.05),the apoptosis rate and Bax protein level decreased obviously(P < 0.05);PM eliminated the inhibitory effect of H⁃Lid on the malignant biological behavior of U87 cells. The survival number of transplanted tumor mice increased after Lid treatment,while the survival number of transplanted tumor mice decreased after PM treatment,and the number in H⁃Lid+PM group was the same as that in L⁃Lid group. Conclusion Lid may inhibit the proliferation of U87 cells, promote cell apoptosis,and then inhibit the progression of glioma by down⁃regulating SHH/GLI signal pathway. 

Key words: lidocaine; SHH/GLI signal pathway; glioma; proliferation; apoptosis ,