Ginkgolide B regulates the proliferation, migration, apoptosis, and epithelial- mesenchymal transition of liver cancer cells through the PERK/ATF4/CHOP pathway

LIU Yanhua1; WANG Hongjuan1; BAO Bojun1; ZHU Junya1; YI Nan1; JI Yifei1; HUANG Wei1; ZHANG Li1; LIU Guoliang2

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Ginkgolide B regulates the proliferation, migration, apoptosis, and epithelial- mesenchymal transition of liver cancer cells through the PERK/ATF4/CHOP pathway

VernacularTitle:银杏内酯B经PERK/ATF4/CHOP通路调控肝癌细胞增殖、迁移、凋亡和EMT
Author: LIU Yanhua1 ^{1
,

2} ; WANG Hongjuan1 ^{1
,

2} ; BAO Bojun1 ^{1
,

2} ; ZHU Junya1 ^{1
,

2} ; YI Nan1 ^{1
,

2} ; JI Yifei1 ^{1
,

2} ; HUANG Wei1 ^{1
,

2} ; ZHANG Li1 ^{1
,

2} ; LIU Guoliang2 ^{1
,

2}
Author Information

1. Department of Gastroenterology, Nantong University Affiliated Hospital, Nantong 226000, Jiangsu, China;
2. Department of Gastroenterology, the Third People's Hospital of Yancheng City & the Sixth Affiliated Hospital of Nantong University, Yancheng 224000, Jiangsu, China
Publication Type:Journal Article
Keywords: 银杏内酯B；蛋白激酶R样内质网激酶/转录激活子4/C/EBP同源蛋白通路；肝癌；增殖；迁移；凋亡；上皮间质转化
From: Chinese Journal of Cancer Biotherapy 2026;33(1):51-58
CountryChina
Language:Chinese
Abstract: [摘要] 目的：探究银杏内酯B（GKB）调控蛋白激酶R样内质网激酶（PERK）/转录激活子4（ATF4）/C/EBP同源蛋白（CHOP）信号通路对肝癌细胞增殖、迁移、凋亡和上皮间质转化（EMT）的影响。方法：将人肝癌细胞MHCC-97H随机分为对照组、GKB组、GSK2656157（PERK抑制剂）组和GKB + GSK2656157组，以GKB和GSK2656157分别干预后，采用MTT法和EdU染色检测各组细胞的增殖活性及增殖率，划痕愈合实验、流式细胞术分别检测各组细胞的迁移及凋亡水平，WB法检测各组细胞中EMT和PERK/ATF4/CHOP信号通路相关蛋白的表达水平。构建MHCC-97H细胞裸鼠移植瘤模型，以同法分组及药物干预后测定各组移植瘤体积，采用免疫组化、TUNEL染色分别检测各组肿瘤细胞增殖、凋亡水平，WB法检测各组移植瘤组织中EMT和PERK/ATF4/CHOP信号通路相关蛋白的表达水平。结果：与对照组比较，GKB组细胞活性、增殖率、迁移率、移植瘤体积、Ki-67阳性细胞率、MMP2、N-cadherin与MMP9蛋白表达均显著降低（均P < 0.05），细胞凋亡率、TUNEL阳性细胞率、p-PERK/PERK与E-cadherin、ATF4、CHOP蛋白表达均显著升高（均P < 0.05）；GSK2656157组各指标变化与GKB组相反（均P < 0.05）。与GKB组比较，GKB + GSK2656157组细胞活性、增殖率、迁移率、移植瘤体积、Ki-67阳性细胞率、MMP2、N-cadherin与MMP9蛋白表达均显著升高（均P < 0.05），细胞凋亡率、TUNEL阳性细胞率、p-PERK/PERK与E-cadherin、ATF4、CHOP蛋白表达均显著降低（均P < 0.05）。结论：GKB可通过激活PERK/ATF4/CHOP信号通路抑制肝癌MHCC-97H细胞增殖、迁移和EMT并促进其凋亡。