摘要
Background:The epithelial-to-mesenchymal transition(EMT)status is associated with programmed death-1 ligand 1(PDL1)expression in various cancers.However,the role and molecular mechanism of PD-L1 in the EMT of sorafenib-resistant hepatocellular carcinoma(HCC)cells remain elusive.In this study,we aimed to investigate the regulation of PD-L1 on the EMT in sorafenib-resistant HCC cells.Methods:Initially,the sorafenib-resistant HCC cell lines HepG2 SR and Huh7 SR were established.Western-blot assays were used to detect the expression of PD-L1,E-cadherin,and N-cadherin.The intervention and overexpression of PD-L1 were used to explore the role of PD-L1 in the regulation of EMT in HepG2 SR and Huh7 SR cells.Cell migration and invasion were assessed by transwell assays.PD-L1 or Sterol regulatory element-binding protein 1(SREBP-1)overexpression and knockdown were performed in order to study the mechanism of PD-L1 in sorafenib-resistant HCC cells.Results:PD-L1 expression was upregulated,whereas E-cadherin levels were downregulated and N-cadherin expression was increased in HepG2 SR and Huh7 SR cells.The cell viabilities of HepG2 and Huh7 cells were lower than those of HepG2 SR and Huh7 SR cells.PD-L1 overexpression reduced E-cadherin expression and increased N-cadherin levels,whereas PD-L1 knock-down increased E-cadherin expression and decreased N-cadherin expression.PD-L1 expression promoted EMT and the migratory and invasive abilities of HepG2 SR and Huh7 SR cells.PD-L1 promoted the EMT of sorafenib-resistant HCC cells via the PI3K/Akt pathway by activating SREBP-1 expression in HepG2 SR and Huh7 SR cells.Conclusions:The findings reveal that PD-L1 expression promotes EMT of sorafenib-resistant HCC cells.
背景:在多种癌症中均可观察到上皮-间质转化(EMT)与程序性死亡配体1(PD-L1)表达之间的相关性。然而,PD-L1在索拉非尼耐药的肝癌细胞EMT中的作用及分子机制尚不清楚。本研究旨在探讨PD-L1对索拉非尼耐药肝癌细胞EMT的调控。方法:首先建立索拉非尼耐药的肝癌细胞株HepG2 SR和Huh7 SR。Western blot法检测PD-L1、E-cadherin和N-cadherin的表达。通过对PD-L1的干预和过表达,探讨PD-L1在HepG2 SR和Huh7 SR肝癌细胞中对EMT的调控。Transwell法检测细胞迁移和侵袭能力。通过过表达和敲除PD-L1或SREBP-1来研究PD-L1在索拉非尼耐药肝癌细胞中的作用机制。结果:HepG2 SR和Huh7 SR细胞株中PD-L1表达上调,E-cadherin表达下调,N-cadherin表达上调。HepG2和Huh7细胞株存活率低于HepG2 SR和Huh7 SR细胞株。PD-L1过表达可使E-cadherin表达下调和N-cadherin表达上调,而PD-L1敲除则上调E-cadherin表达和下调N-cadherin表达。PD-L1的表达促进了HepG2 SR和Huh7 SR细胞株的EMT和侵袭能力。PD-L1促进索拉非尼耐药肝癌细胞(HepG2 SR和Huh7 SR)EMT是通过激活SREBP-1表达从而启动PI3K/Akt通路实现的。结论:本实验结果显示PD-L1可促进索拉非尼耐药肝癌细胞的EMT。
基金
supported by Natural Science Foundation of China[No.81771945].
