Exp Mol Med.
2012 Nov;44(11):633-641.
Triptolide inhibits ovarian cancer cell invasion by repression of matrix metalloproteinase 7 and 19 and upregulation of E-cadherin
- Affiliations
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- 1Department of Gynaecology and Obstetrics, Tangdu Hospital, Fourth Military Medical University, Xi'an 710038, China.
- 2Department of Pharmaceutics, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China.
- 3Department of Health and Service, School of Military Preventive Medicine, Fourth Military Medical University, Xi'an 710032, China.
- 4Key Laboratory of Gastrointestinal Pharmacology of Chinese Materia, Medica of the State Administration of Traditional Chinese Medicine, Department of Pharmacology, School of Pharmacy, Fourth Military Medical University, Xi'an 710032, China. zhipengw@fmmu.
Abstract
- 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.
Keyword
MeSH Terms
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Animals
Antineoplastic Agents, Alkylating/*pharmacology
Cadherins/*genetics/metabolism
Cell Line, Tumor
Cell Movement/drug effects
Cell Proliferation/drug effects
Cystadenocarcinoma, Serous/*drug therapy/pathology
Diterpenes/*pharmacology
Epoxy Compounds/pharmacology
Female
Gene Expression Regulation, Enzymologic/drug effects
Humans
Matrix Metalloproteinase 7/genetics/*metabolism
Matrix Metalloproteinases, Secreted/genetics/*metabolism
Mice
Mice, Inbred BALB C
Mice, Nude
Neoplasm Invasiveness
Ovarian Neoplasms/*drug therapy
Paclitaxel/pharmacology
Phenanthrenes/*pharmacology
Promoter Regions, Genetic
Up-Regulation/drug effects
Xenograft Model Antitumor Assays
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