Anti-metastasis traditional Chinese medicine monomer screening system based on perinucleolar compartment analysis in hepatocellular carcinoma cells

摘要

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.