艾司氯胺酮调节Wnt/β-catenin信号通路对肝癌细胞增殖、迁移和侵袭的影响

doi:10.3969/j.issn.1005-6483.20240083

摘要/Abstract

摘要： 目的探讨艾司氯胺酮(S-KET)对肝癌细胞增殖、迁移和侵袭及Wnt/β-连环蛋白(β-catenin)信号通路的影响。方法将肝癌细胞Hep G2分为对照组(Control组)、艾司氯胺酮低、中、高浓度处理组(S-KET-L、S-KET-M、S-KET-H组)、艾司氯胺酮高浓度处理+Wnt激活剂氯化锂组(S-KET-H+LiCl组)；Edu检测细胞增殖；划痕实验检测细胞迁移；Transwell实验检测细胞侵袭；Western blot检测细胞核增殖抗原标志物(Ki-67)、细胞周期蛋白D1(Cyclin D1)、基质金属蛋白酶(MMP)-2、基质金属蛋白酶(MMP)-9、Wnt1、β-catenin蛋白表达；裸鼠移植瘤检测艾司氯胺酮对肝癌移植瘤生长的影响；免疫组化检测Wnt1、β-catenin蛋白表达情况。结果与Control组相比，S-KET-L、S-KET-M、S-KET-H组Hep G2细胞Edu阳性率、Ki-67、Cyclin D1、细胞划痕愈合率、细胞侵袭数量、MMP-2、MMP-9、Wnt1、β-catenin蛋白表达显著降低,差异有统计学意义(P<0.05)；与S-KET-H组比较，S-KET-H+LiCl组Hep G2细胞Edu阳性率、Ki-67、Cyclin D1、细胞划痕愈合率、细胞侵袭数量、MMP-2、MMP-9、Wnt1、β-catenin蛋白表达显著升高,差异有统计学意义(P<0.05)；裸鼠移植瘤实验结果显示，与Control组比较，S-KET组小鼠移植瘤生长缓慢，移植瘤质量、体积减小，Wnt1、β-catenin蛋白表达显著降低,差异有统计学意义(P<0.05)。结论艾司氯胺酮可以通过抑制Wnt/β-catenin信号通路抑制肝癌细胞的增殖、迁移与侵袭。

关键词: 艾司氯胺酮, Wnt/β-连环蛋白信号通路, 肝癌细胞, 增殖, 迁移, 侵袭

Abstract: Objective To investigate the effects of Esketamine (S-KET) on the proliferation,migration,invasion,and Wnt/β-catenin signaling pathway of liver cancer cells.Methods Hep G2 liver cancer cells were separated into Control group,low,medium,and high concentration treatment groups (S-KET-L,S-KET-M,S-KET-H groups),and high concentration treatment group (S-KET-H+LiCl group);Edu was applied to detect cell proliferation;scratch experiment was applied to detect cell migration;Transwell experiment was applied to detect cell invasion.Western blot was applied to detect the expression of nuclear proliferation antigen markers (Ki-67),Cyclin D1,matrix metalloproteinase 2 (MMP-2),matrix metalloproteinase 9 (MMP-9),Wnt1,and β-catenin proteins;nude mouse transplanted tumor was applied to detect the effect of Esketamine on the growth of liver cancer transplanted tumors;immunohistochemistry was applied to detect the expression of Wnt1 and β-catenin proteins.Results Compared with the Control group,the Edu positive rate,Ki-67,Cyclin D1,scratch healing rate,number of cell invasions,the expression of MMP-2,MMP-9,Wnt1,and β-catenin proteins in Hep G2 cells in the S-KET-L,S-KET-M,and S-KET-H groups were obviously reduced (P<0.05);compared with the S-KET-H group,the Edu positive rate,Ki-67,Cyclin D1,scratch healing rate,number of cell invasions,the expression of MMP-2,MMP-9,Wnt1,and β-catenin proteins in Hep G2 cells in Hep G2 cells in the S-KET-H+LiCl group were significantly increased (P<0.05);the results of nude mouse tumor transplantation experiment showed that compared with the Control group,the S-KET group mice showed slow tumor growth,reduced tumor mass and volume,and significantly reduced expression of Wnt1 and β-catenin proteins (P<0.05).Conclusion Esketamine can inhibit the proliferation,migration,and invasion of liver cancer cells by inhibiting the Wnt/β-catenin signaling pathway.

Key words: esketamine, Wnt/β-catenin signaling pathway, liver cancer cells, proliferation, migration, invasion

王振云, 王洪涛, 周瑞欣, 张津广. 艾司氯胺酮调节Wnt/β-catenin信号通路对肝癌细胞增殖、迁移和侵袭的影响[J]. 临床外科杂志, 2025, 33(4): 433-437.

WANG Zhenyun, WANG Hongtao, ZHOU Ruixin, ZHANG Jinguang. Effects of Esketamine on the proliferation,migration,and invasion of liver cancer cells by regulating the Wnt/β-catenin signaling pathway[J]. JOURNAL OF CLINICAL SURGERY, 2025, 33(4): 433-437.

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