CD147 is increased in HCC cells under starvation and reduces cell death through upregulating p-mTOR in vitro
CD147 is increased in HCC cells under starvation and reduces cell death through upregulating p-mTOR in vitro
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CD147 在饥饿条件下的 HCC 细胞中增加，并通过体外上调 p-mTOR 减少细胞死亡
DOI：
10.1007/s10495-015-1189-y
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发表时间：
2016-01-01
期刊：
影响因子：
7.2
通讯作者：
Chen, Yanke
中科院分区：
文献类型：
--
作者：
Gou, Xingchun;Tang, Xu;Chen, Yanke
经动脉化疗栓塞（TACE）是治疗中间型肝细胞癌（HCC）的标准治疗方法，然而，参与TACE后HCC细胞存活和肿瘤转移的关键分子仍不清楚。CD 147是免疫球蛋白超家族的成员，在HCC细胞表面过表达，与HCC患者的恶性潜能和不良预后相关。在这项研究中，使用Earle平衡盐溶液培养基培养模型，模拟TACE诱导的营养剥夺，我们研究了饥饿条件下HCC细胞上CD 147表达的调节及其对HCC细胞死亡的功能影响。在饥饿的早期阶段，CD 147在SMMC 7721、HepG 2和HCC 9204肝癌细胞系中的表达在蛋白水平上显著上调。通过特异性小干扰RNA（siRNA）下调CD 147显著促进饥饿诱导的细胞死亡。此外，在饥饿条件下，与对照siRNA转染的细胞相比，CD 147 siRNA转染的SMMC 7721细胞表现出显著增加的凋亡和自噬水平，而在正常培养条件下，两个处理组之间没有观察到差异。此外，CD 147的沉默导致饥饿SMMC 7721细胞中磷酸化的哺乳动物雷帕霉素靶蛋白（p-mTOR）显著下调。最后，饥饿和抗CD 147单克隆抗体的联合处理显示出协同的肝癌细胞杀伤作用。我们的研究表明，在饥饿条件下上调CD 147可能通过mTOR信号调节凋亡和自噬来减少肝癌细胞死亡，并且CD 147可能是提高TACE疗效的新的潜在分子靶点。
Transarterial chemoembolization (TACE) is the standard of care for treatment of intermediate hepatocellular carcinoma (HCC), however, key molecules involved in HCC cell survival and tumor metastasis post-TACE remain unclear. CD147 is a member of the immunoglobulin superfamily that is overexpressed on the surface of HCC cells and is associated with malignant potential and poor prognosis in HCC patients. In this study, using an Earle’s Balanced Salt Solution medium culture model that mimics nutrient deprivation induced by TACE, we investigated the regulation of CD147 expression on HCC cells under starvation conditions and its functional effects on HCC cell death. During early stages of starvation, the expression of CD147 was considerably upregulated in SMMC7721, HepG2 and HCC9204 hepatoma cell lines at the protein levels. Downregulation of CD147 by specific small interfering RNA (siRNA) significantly promoted starvation-induced cell death. In addition, CD147 siRNA-transfected SMMC7721 cells demonstrated significantly increased levels of both apoptosis and autophagy as compared to cells transfected with control siRNA under starvation conditions, whereas no difference was observed between the two treatment groups under normal culture conditions. Furthermore, silencing of CD147 resulted in a remarkable downregulation of phosphorylated mammalian target of rapamycin (p-mTOR) in starved SMMC7721 cells. Finally, the combined treatment of starvation and anti-CD147 monoclonal antibody exhibited a synergistic HCC cell killing effect. Our study suggests that upregulation of CD147 under starvation may reduce hepatoma cell death by modulating both apoptosis and autophagy through mTOR signaling, and that CD147 may be a novel potential molecular target to improve the efficacy of TACE.