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Lentivirus-mediated RNA silencing of c-Met markedly suppresses peritoneal dissemination of gastric cancer in vitro and in vivo.
MedLine Citation:
PMID:  22407230     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Aim:To investigate the expression of c-Met in peritoneal free cancer cells isolated from human gastric cancer ascites, and its relationship to peritoneal dissemination of gastric cancer.Methods:Peritoneal free cancer cells (PFCCs) were isolated from ascites specimens of gastric cancer patients. c-Met expression in PFCCs was detected with immunocytochemistry. In human gastric cancer cell line SGC7901, c-Met expression was detected using RT-PCR and Western blot, and was suppressed with lentivirus-mediated RNAi. The proliferation of SGC7901 cells was measured using MTT assay, and the invasion ability was detected with invasion assay. The adhesion of SGC7901 cells to peritoneum was observed in human peritoneal mesothelial cells (HPMCs) monolayer in vitro and in mice in vivo.Results:PFCCs were isolated from ascites of 6 out of 10 gastric cancer patients. c-Met expression in PFCCs was detected in 5 of the 6 gastric cancer patients. In SGC7901 cells, Lentivirus-mediated RNAi significantly reduced both c-Met mRNA and protein expression, which resulted in suppressing the cell proliferation, invasion and adhesion to peritoneum. The expression of α3β1 integrin and E-cadherin was significantly inhibited in SGC7901 cells transfected with Lenti-miRNAc-Met. In the peritoneal dissemination model of gastric cancer, intraperitoneal injection of Lenti-miRNAc-Met markedly suppressed the tumor regression of SGC7901 cells.Conclusion:c-Met is expressed in PFCCs from the ascites of gastric cancer patients. Down-regulation of c-Met expression markedly suppresses the multistep process of peritoneal dissemination, thus may be a potential target for the treatment of gastric cancer.
Authors:
Xiao-Lei Wang; Xi-Mei Chen; Jian-Ping Fang; Chang-Qin Yang
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-3-12
Journal Detail:
Title:  Acta pharmacologica Sinica     Volume:  -     ISSN:  1745-7254     ISO Abbreviation:  -     Publication Date:  2012 Mar 
Date Detail:
Created Date:  2012-3-12     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100956087     Medline TA:  Acta Pharmacol Sin     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Department of Gastroenterology, Institute of Digestive Disease, Tongji Hospital affiliated to Tongji University, Shanghai 200065, China.
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