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Experimental & Molecular Medicine ; : 633-641, 2012.
Artigo em Inglês | WPRIM | ID: wpr-149765

RESUMO

Triptolide, a compound extracted from the traditional Chinese medicine preparation of Tripterygium wilfordii Hook F., has been reported to have anti-inflammatory and anti-cancer activities. However, its effect on ovarian cancer invasion is unknown. We observed that MMP7 and MMP19 expression increased in ovarian cancer tissue. Triptolide treatment inhibited the migration and invasion of ovarian cancer cells SKOV3 and A2780 at the concentration of 15 nM. We also observed that triptolide suppressed MMP7 and MMP19 promoter activity in a dose-dependent manner, down-regulating the expressions of these promoters on mRNA and protein level. Moreover, triptolide enhanced E-cadherin expression in ovarian cancer cells. In vivo, triptolide inhibited tumor formation and metastasis in nude mice, and suppressed MMP7 and MMP19 expression; it also enhanced E-cadherin expression in tumor in a dose-dependent manner. Over expression of MMP7 and MMP19, or suppression of E-cadherin expression partially abolished the inhibitory effect of triptolide on invasion of ovarian cancer cells. To summarize, triptolide significantly inhibited the migration and invasion of ovarian cancer cells by suppression of MMP7 and MMP19 and up-regulation of E-cadherin expression. This study shows that triptolide is a good candidate for the treatment of ovarian cancer and reduction of metastasis.


Assuntos
Animais , Feminino , Humanos , Camundongos , Antineoplásicos Alquilantes/farmacologia , Caderinas/genética , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Cistadenocarcinoma Seroso/tratamento farmacológico , Diterpenos/farmacologia , Compostos de Epóxi/farmacologia , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Metaloproteinase 7 da Matriz/genética , Metaloproteinases da Matriz Secretadas/genética , Camundongos Endogâmicos BALB C , Camundongos Nus , Invasividade Neoplásica , Neoplasias Ovarianas/tratamento farmacológico , Paclitaxel/farmacologia , Fenantrenos/farmacologia , Regiões Promotoras Genéticas , Regulação para Cima/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto
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