Inhibitory effect of anti-hepatitis drug bicyclol on invasion of human hepatocellular carcinoma MHCC97-H cells with high metastasis potential and its relative mechanisms.
To assess the anti-invasion effect of bicyclol (1) and its mechanism in human hepatocellular carcinoma (HCC) MHCC97-H cells with high metastatic potential. MTT assay was performed to evaluate the cytotoxicity of 1 to MHCC97-H cells and its inhibitory effect on the adhesion of these cells to laminin (LN) and fibronectin (FN). The anti-invasion effect of 1 was detected in an experiment using a transwell chamber. Transcription of vascular endothelial growth factor (VEGF), nm23-H1, and urokinase-type plasminogen activator receptor (uPAR) mRNAs was determined by an RT-PCR assay. The secretion and expression of alpha-fetoprotein (AFP) were analyzed by ELISA and flow cytometry, respectively. At concentrations of 10, 50, and 100 mumol/l, 1 obviously inhibited the adhesion of the MHCC97-H cells to LN and FN. The rates of inhibition of MHCC97-H cell invasion by 50 and 100 mumol/l for 1 were 37.3 and 50.2%, respectively. Drug 1 also decreased the expressions of VEGF, nm23-H1, and uPAR mRNA and the secretion of AFP in MHCC97-H cells. At low cytotoxic concentrations, the anti-hepatitis drug 1 demonstrated a significant anti-invasive effect in human HCC MHCC97-H cells with high metastatic potential. The inhibition of the expressions of VEGF, nm23-H1, and uPAR should contribute, at least in part, to the anti-invasion property of 1.
Sun
Hua
H
Department of Pharmacology, Institute of Materia Medica, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.
Liu
Geng-Tao
GT
D001713:Biphenyl Compounds / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000473:pathology*; D002448:Cell Adhesion / Q000187:drug effects; D006505:Hepatitis / Q000188:drug therapy*; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D015394:Molecular Structure; D009361:Neoplasm Invasiveness / Q000473:pathology; D009362:Neoplasm Metastasis / Q000473:pathology; D012689:Sequence Homology, Nucleic Acid; D014407:Tumor Cells, Cultured; D014568:Urokinase-Type Plasminogen Activator / Q000235:genetics; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics; D000509:alpha-Fetoproteins / Q000378:metabolism
D001713:Biphenyl Compounds; D042461:Vascular Endothelial Growth Factor A; D000509:alpha-Fetoproteins; C477843:bicyclol; D014568:Urokinase-Type Plasminogen Activator