索拉菲尼耐药肝癌细胞株PD-L1表达上调促进上皮-间质转化

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。

C_(21) Steroidal Glycosides from Acidic Hydrolysate of Cynanchum otophyllum

Objective To investigate the structures of compounds in the rhizome of Cynanchum otophyllum（Asclepiadaceae）, and to find new C21 steroidal glycosides. Methods The ethyl acetate extract from the rhizome was subjected to acidic hydrolysis and isolated by column chromatography; The structures of the purified compounds were determined by spectral methods. Literature search confirmed whether those compounds were of new structures. Results Three compounds were isolated and their structures were deacetylmetaplexigenin 3-O-β-D-oleandropyranosyl-（1→4）-α-D-oleandropyranosyl-（1→4）-α-D-oleandropyranoside（1）, deacetylmetaplexigenin 3-O-α-D-oleandropyranosyl-（1→4）-β-D-thevetopyranosyl-（1→4）-α-D-oleandropyranoside（2）, and deacetylmeta-plexigenin 3-O-β-D-cymaropyranosyl-（1→4）-α-D-oleandropyranoside（3）, respectively. Conclusion Compounds 1-3 are new compounds.