Document Detail


Overexpression of TIMP-1 mediated by recombinant adenovirus in hepatocellular carcinoma cells inhibits proliferation and invasion in vitro.
MedLine Citation:
PMID:  16911941     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Matrix metalloproteinases (MMPs) and its natural tissue inhibitors of metalloproteinases (TIMPs) are involved in cancer progression. This study was undertaken to determine the effects of overexpression of TIMP-1 on human hepatocellular carcinoma (HCC) cell growth, proliferation, and invasion. METHODS: Employing the efficient AdEasy(TM) system, recombinant adenovirus AdTIMP-1 containing full-length cDNA of TIMP-1 was generated by homologous recombination and amplified in 293 cells. Then, human HCC cell line (HepG2) underwent gene transfection to overexpress TIMP-1 (so-called HepG-T cells). The mRNA and protein expressions of TIMP-1 were detected with RT-PCR and Western blotting, respectively. The ultrastructure was observed with a transmission electron microscope and the proliferation of HepG-T cells was determined by MTT assay and growth curve. The potential of in vitro invasion was measured with Millicell Chamber. RESULTS: The resulting AdTIMP-1 and HepG-T cells were generated and the expression of TIMP-1 was detected in vitro. The cell proliferation curves and MTT assay showed HepG-T cells' growth, and proliferation were obviously inhibited. The invasion across Matrigel-coated filters was significantly decreased compared with controls. The suppression rate of HepG-2 cells with AdhTIMP-1 transfection was 50%, and AdhTIMP-1 transfection inhibited by more than 91.6% of the invasion into the Matrigel-coated filter (P<0.01). CONCLUSIONS: TIMP-1 overexpression results in the suppression of proliferative and invasive potential of HepG2 cells in vitro. This study demonstrates the potential role of TIMP-1 as a target for liver cancer gene therapy and has laid a foundation for further study on its anticancer function.
Authors:
Dong Xia; Lu-Nan Yan; Jian-Guo Xie; Yu Tong; Mao-Lin Yan; Xin-Ping Wang; Ming-Man Zhang; Lan-Ying Zhao
Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Hepatobiliary & pancreatic diseases international : HBPD INT     Volume:  5     ISSN:  1499-3872     ISO Abbreviation:  HBPD INT     Publication Date:  2006 Aug 
Date Detail:
Created Date:  2006-08-16     Completed Date:  2006-12-19     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101151457     Medline TA:  Hepatobiliary Pancreat Dis Int     Country:  China    
Other Details:
Languages:  eng     Pagination:  409-15     Citation Subset:  IM    
Affiliation:
Department of General Surgery, West China Hospital, Sichuan University, Chengdu 610041, China.
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MeSH Terms
Descriptor/Qualifier:
Adenoviridae / genetics,  physiology*
Base Sequence
Blotting, Western
Carcinoma, Hepatocellular / metabolism*,  pathology
Cell Line, Tumor
Cell Proliferation*
DNA Primers
Humans
Liver Neoplasms / metabolism*,  pathology
Microscopy, Electron, Transmission
Neoplasm Invasiveness*
RNA, Messenger / genetics
Recombination, Genetic
Reverse Transcriptase Polymerase Chain Reaction
Tissue Inhibitor of Metalloproteinase-1 / genetics,  metabolism*
Chemical
Reg. No./Substance:
0/DNA Primers; 0/RNA, Messenger; 0/Tissue Inhibitor of Metalloproteinase-1

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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