MMI-166, a selective matrix metalloproteinase inhibitor, promotes apoptosis in human pancreatic cancer.
Med Oncol
; 32(1): 418, 2015 Jan.
Article
em En
| MEDLINE
| ID: mdl-25471789
ABSTRACT
MMI-166 is a third-generation selective matrix metalloproteinase (MMP) inhibitor that prevents tumor invasion and metastasis by downregulating the activity of MMP-2 and MMP-9. However, MMI-166's effect in pancreatic cancer cells has not been widely studied. Initially, we treated SW1990, human pancreatic cancer cells, with 0, 50 or 100 µg/ml of MMI-166 for 24 h. Apoptosis in the cells was then observed by inverted fluorescence microscope and flow cytometry; the apoptosis rate was dependent on MMI-166 concentration. We then injected nude mice with SW1990 cells. Volume of the resulting xenograft tumors in nude mice treated with MMI-166 was far less than that of the control group, whereas their apoptotic index was much greater. Expression of MMP-2, MMP-9, c-myc and survivin were markedly lower in tumors from the treated mice than in the control group. In cell experiments, MMP-2 and MMP-9 activities were downregulated by MMI-166 compared with controls, as were both mRNA and protein levels of MMP-2, MMP-9 and c-myc, although survivin expression did not differ. These results show that MMI-166 can induce apoptosis of pancreatic cancer cells in vitro and in vivo. The mechanism may be related to downregulation of c-myc by MMI-166.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Pancreáticas
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Sulfonamidas
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Apoptose
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Inibidores de Metaloproteinases de Matriz
Limite:
Animals
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Humans
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Male
Idioma:
En
Revista:
Med Oncol
Assunto da revista:
NEOPLASIAS
Ano de publicação:
2015
Tipo de documento:
Article