Liu Feifei, Lou Guohua, Zhang Tianbao, Chen Senzhong, Xu Jia, Xu Lichen, Huang Chunhong, Liu Yanning, Chen Zhi
State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University Hangzhou 310003, China.
Am J Transl Res. 2019 Jun 15;11(6):3555-3566. eCollection 2019.
Hepatocellular Carcinoma (HCC) lacks effective anti-metastasis drugs. Traditional Chinese Medicine (TCM) monomers have shown anti-proliferation activity in HCC, but few of them are specifically anti-metastasis. Therefore, further clarifying the indicators of HCC metastasis and screening TCM monomers based on the indicators, will effectively guide the development of novel anti-HCC drugs. The perinucleolar compartment (PNC), existing in the nuclear of tumor cells, is closely correlated with metastasis of several tumors. In this study, we found positive correlation between higher PNC prevalence and metastasis in HCC tissue of patients. The PNC prevalence was also positively correlated with the malignancy of HCC cell lines. On this premise, we established a PNC-based screening system for anti-metastasis TCM monomers and obtained Camptothecin (CPT), Evodiamine and Isoglycyrrhizin, the three most effective TCM monomers from a TCM monomer library to reduce the PNC prevalence in Huh7 cells. The anti-metastasis effect of these TCM monomers was positively correlated with their PNC inhibitor effect. Our data further revealed that CPT reduced metastasis of Huh7 cells possibly by inhibiting Epithelial-Mesenchymal Transition by upregulating the expression of ZO-1, E-cadherin and Claudin-1. The PNC-based screening system is effective and it may provide an effective technical platform for the development of anti-metastasis drugs.
肝细胞癌（HCC）缺乏有效的抗转移药物。中药单体在HCC中已显示出抗增殖活性，但其中很少有专门抗转移的。因此，进一步阐明HCC转移的指标并基于这些指标筛选中药单体，将有效地指导新型抗HCC药物的开发。核仁周区（PNC）存在于肿瘤细胞的细胞核中，与多种肿瘤的转移密切相关。在本研究中，我们发现患者HCC组织中较高的PNC发生率与转移呈正相关。PNC发生率也与HCC细胞系的恶性程度呈正相关。在此前提下，我们建立了基于PNC的抗转移中药单体筛选系统，并从中药单体库中获得了喜树碱（CPT）、吴茱萸碱和异甘草酸镁，这三种最有效的中药单体可降低Huh7细胞中的PNC发生率。这些中药单体的抗转移作用与其PNC抑制作用呈正相关。我们的数据进一步表明，CPT可能通过上调ZO-1、E-钙黏蛋白和Claudin-1的表达来抑制上皮-间质转化，从而降低Huh7细胞的转移。基于PNC的筛选系统是有效的，它可能为抗转移药物的开发提供一个有效的技术平台。
