PMID- 15993560
OWN - NLM
STAT- MEDLINE
DCOM- 20060119
LR  - 20131121
IS  - 0748-7983 (Print)
IS  - 0748-7983 (Linking)
VI  - 31
IP  - 9
DP  - 2005 Nov
TI  - Inhibition of matrix metalloproteinase activity and growth of gastric 
      adenocarcinoma cells by an angiotensin converting enzyme inhibitor in in vitro 
      and murine models.
PG  - 1042-50
AB  - INTRODUCTION: Angiotensin converting enzyme (ACE) shares structural homology with 
      the matrix metalloproteinase family of proteolytic enzymes (MMPs) responsible for 
      degradation of the extracellular matrix (ECM). ACE inhibitors have been reported 
      to protect against cancer in patients. The aim of this study was to determine 
      whether the ACE inhibitor, captopril, could impair the activity of MMPs and 
      impact on tumour invasion and growth in a cell line and murine model. METHODS: 
      For proof of principle, the protein activity of human MMP-2 and MMP-9 produced by 
      the HT1080 fibrosarcoma cell line was detected using gelatin zymography. Gene 
      expression was determined by real time reverse transcriptase PCR and tumour cell 
      invasion using Matrigel invasion chambers. The effect of captopril on the in vivo 
      growth of MGLVA-1 human gastric adenocarcinoma xenografts was evaluated in a nude 
      mouse model. RESULTS: Captopril inhibited activity of secreted MMP-9 and MMP-2, 
      however, gene expression in HT1080 remained unaltered. Invasion of HT1080 cells 
      was inhibited by 48% (p<0.001). Tumour size was reduced by 40-50% with 0.4 mg/ml 
      captopril (p<0.01) and when combined with cisplatin the inhibition increased to 
      71% (p<0.05). DISCUSSION: ACE inhibitors inhibit the activity of secreted MMP-2 
      and -9 by a mechanism similar to synthetic MMP inhibitors. ACE inhibitors have 
      previously been shown to inhibit tumour growth, however; this is the first study 
      to demonstrate inhibition of a human gastric xenograft, both alone and in 
      combination with cisplatin. These results support further investigation into the 
      anticancer effects of ACE inhibitors.
FAU - Williams, R N
AU  - Williams RN
AD  - Academic Unit of Cancer Studies, D Floor, West Block, QMC, University Hospital, 
      Nottingham NG7 2UH, UK.
FAU - Parsons, S L
AU  - Parsons SL
FAU - Morris, T M
AU  - Morris TM
FAU - Rowlands, B J
AU  - Rowlands BJ
FAU - Watson, S A
AU  - Watson SA
LA  - eng
PT  - Journal Article
DEP - 20050701
PL  - England
TA  - Eur J Surg Oncol
JT  - European journal of surgical oncology : the journal of the European Society of 
      Surgical Oncology and the British Association of Surgical Oncology
JID - 8504356
RN  - 0 (Angiotensin-Converting Enzyme Inhibitors)
RN  - 0 (Matrix Metalloproteinase Inhibitors)
RN  - 9G64RSX1XD (Captopril)
RN  - EC 3.4.24.24 (Matrix Metalloproteinase 2)
RN  - EC 3.4.24.35 (Matrix Metalloproteinase 9)
SB  - IM
MH  - Adenocarcinoma/enzymology/*pathology
MH  - Angiotensin-Converting Enzyme Inhibitors/*pharmacology
MH  - Animals
MH  - Captopril/*pharmacology
MH  - Dose-Response Relationship, Drug
MH  - Female
MH  - Humans
MH  - Matrix Metalloproteinase 2/*metabolism
MH  - Matrix Metalloproteinase 9/*metabolism
MH  - Matrix Metalloproteinase Inhibitors
MH  - Mice
MH  - Mice, Nude
MH  - Neoplasm Transplantation
MH  - Stomach Neoplasms/enzymology/*pathology
MH  - Tumor Cells, Cultured/enzymology/pathology
EDAT- 2005/07/05 09:00
MHDA- 2006/01/20 09:00
CRDT- 2005/07/05 09:00
PHST- 2004/08/11 00:00 [received]
PHST- 2005/04/26 00:00 [accepted]
PHST- 2005/07/05 09:00 [pubmed]
PHST- 2006/01/20 09:00 [medline]
PHST- 2005/07/05 09:00 [entrez]
AID - S0748-7983(05)00126-5 [pii]
AID - 10.1016/j.ejso.2005.04.003 [doi]
PST - ppublish
SO  - Eur J Surg Oncol. 2005 Nov;31(9):1042-50. doi: 10.1016/j.ejso.2005.04.003. Epub 
      2005 Jul 1.