SDC1 promotes cisplatin resistance in hepatic carcinoma cells via PI3K-AKT pathway
SDC1 promotes cisplatin resistance in hepatic carcinoma cells via PI3K-AKT pathway
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DOI：
10.1007/s13577-020-00362-6
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发表时间：
2020-04-20
期刊：
影响因子：
4.3
通讯作者：
Yu, Zhongshan
中科院分区：
文献类型：
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作者：
Yu, Liquan;Xu, Hong;Yu, Zhongshan
本研究旨在探讨Syndecan 1（SDC 1）在肝癌顺铂耐药中的作用。细胞增殖和活力分别通过直接计数和3-（4，5-二甲基噻唑-2-基）-2，5-二苯基溴化四唑测定来测定。SDC 1、p-AKT、AKT和β-肌动蛋白的蛋白水平通过蛋白质印迹法定量。SDC 1转录丰度通过实时聚合酶链反应测定。应用免疫组化方法分析SDC 1在临床肝肿瘤组织中的相对表达。SDC 1在顺铂耐药的HepG 2细胞中上调（下文表示为HepG 2 CR）。SDC 1敲低使HepG 2 CR细胞对顺铂治疗重新敏感。SDC 1的异位过表达赋予初始HepG 2细胞耐药性。PI 3 K/AKT通路在HepG 2 CR细胞中被过度激活，同时给予PI 3 K抑制剂可大大克服耐药性。我们还证明了SDC 1在临床肝细胞癌样本中异常上调。我们的研究强调了SDC 1-PI 3 K/AKT信号在肝细胞癌顺铂耐药中的重要性。
This study is to analyze the potential contribution of Syndecan 1 (SDC1) to cisplatin resistance in hepatic carcinoma. Cell proliferation and viability were determined by direct counting and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, respectively. The protein levels of SDC1, p-AKT, AKT and beta-actin were quantified by western blotting. The SDC1 transcript abundance was measured by real-time polymerase chain reaction. The relative expression of SDC1 in clinical liver tumor samples was analyzed with immunohistochemistry. SDC1 was up-regulated in cisplatin-resistant HepG2 cells (denoted as HepG2 CR hereafter). SDC1-knockdown re-sensitized HepG2 CR cells to cisplatin treatment. Ectopic over-expression of SDC1 conferred drug resistance to naive HepG2 cells. PI3K/AKT pathway was over-activated in HepG2 CR cells, and simultaneous administration with PI3K inhibitor greatly surmounted the resistance. We also demonstrated that SDC1 was aberrantly up-regulated in clinical hepatocellular carcinoma samples. Our study highlighted the importance of SDC1-PI3K/AKT signaling in the cisplatin resistance in hepatocellular carcinoma.