[Inhibitory effect of dimethyl dicarboxylate biphenyl on invasion of human hepatocellular carcinoma cell line MHCC97-H with high metastasis potential and its mechanisms].
OBJECTIVE
Invasion and metastasis is the main cause of the poor prognosis and high mortality of hepatocellular carcinoma (HCC). Inhibiting invasion and metastasis is an effective approach to reduce the development and mortality of HCC. Dimethyl dicarboxylate biphenyl (DDB) is an old anti-hepatitis drug used in clinics. This study was to assess the inhibitory effect of DDB on adhesion and invasion of HCC cell line MHCC97-H with high metastasis potential, and explore its possible mechanism.


METHODS
MTT assay was used to evaluate the cytotoxicity of DDB to MHCC97-H cells and the inhibitory effect of DDB on the adhesion of MHCC97-H cells to laminin (LN) and fibronectin (FN). The inhibitory effect of DDB on the invasion of MHCC97-H cells was detected by transwell chamber experiment. The mRNA levels of vascular endothelial growth factor (VEGF), nm23-H1, and urokinase-type plasminogen activator receptor (uPAR) were determined by reverse transcription-polymerase chain reaction (RT-PCR). The secretion and expression of alpha fetoprotein (AFP) were analyzed by ELISA and flow cytometry, respectively.


RESULTS
DDB at non-cytotoxic concentrations (10, 50 and 100 micromol/L) obviously inhibited the adhesion of MHCC97-H cells to LN and FN. The inhibition rates of the invasion of MHCC97-H cells were 25.8% and 32.3% after treatment of 50 and 100 micromol/L DDB, respectively; 50 and 100 micromol/L DDB also decreased the mRNA levels of VEGF, nm23-H1, and uPAR in MHCC97-H cells. The inhibition rates of AFP secretion of MHCC97-H cells were 16.5%, 17.5%, and 48.5% after treatment of 50, 100, and 200 micromol/L DDB, respectively; it also decreased the expression of AFP in MHCC97-H cells.


CONCLUSIONS
DDB, at non-cytotoxic concentrations, may obviously suppress the invasion of MHCC97-H cells through inhibiting VEGF, nm23-H1, and uPAR expression.
Sun
Hua
H
Department of Pharmacology, Institute of Materia Medica, Peking Union Medical College & Chinese Academy of Medical Sciences, Beijing, 100050, P. R. China.
Liu
Geng-Tao
GT
D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000473:pathology*; D002448:Cell Adhesion / Q000187:drug effects*; D045744:Cell Line, Tumor; D004149:Dioxoles / Q000494:pharmacology*; D006801:Humans; D054778:NM23 Nucleoside Diphosphate Kinases / Q000378:metabolism; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D012333:RNA, Messenger / Q000378:metabolism; D055293:Receptors, Urokinase Plasminogen Activator / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D000509:alpha-Fetoproteins / Q000378:metabolism
D004149:Dioxoles; D054778:NM23 Nucleoside Diphosphate Kinases; D012333:RNA, Messenger; D055293:Receptors, Urokinase Plasminogen Activator; D042461:Vascular Endothelial Growth Factor A; D000509:alpha-Fetoproteins; C041398:7,7'-dimethoxy-(4,4'-bi-1,3-benzodioxole)-5,5'-dicarboxylic acid dimethyl ester; C517938:NME1 protein, human