Triptolide inhibits ovarian cancer cell invasion by repression of matrix metalloproteinase 7 and 19 and upregulation of E-cadherin.
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.
Department of Gynaecology and Obstetrics, Tangdu Hospital, Fourth Military Medical University, Xi’an 710038, China.
Hongxi
H
Zhao
Zhifu
Z
Yang
Xiaohong
X
Wang
Xianzhi
X
Zhang
Meng
M
Wang
Yukun
Y
Wang
Qibing
Q
Mei
Zhipeng
Z
Wang
D000818:Animals; D015703:Antigens, CD; D018906:Antineoplastic Agents, Alkylating / Q000494:pharmacology*; D015820:Cadherins / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D018284:Cystadenocarcinoma, Serous / Q000188:drug therapy* / Q000473:pathology; D004224:Diterpenes / Q000494:pharmacology*; D004852:Epoxy Compounds / Q000494:pharmacology; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006801:Humans; D020783:Matrix Metalloproteinase 7 / Q000235:genetics / Q000378:metabolism*; D053505:Matrix Metalloproteinases, Secreted / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D017239:Paclitaxel / Q000494:pharmacology; D010616:Phenanthrenes / Q000494:pharmacology*; D011401:Promoter Regions, Genetic; D015854:Up-Regulation / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
D015703:Antigens, CD; D018906:Antineoplastic Agents, Alkylating; C513384:CDH1 protein, human; D015820:Cadherins; D004224:Diterpenes; D004852:Epoxy Compounds; D010616:Phenanthrenes; C001899:triptolide; D053505:Matrix Metalloproteinases, Secreted; C108362:matrix metalloproteinase 19; C060932:MMP7 protein, human; D020783:Matrix Metalloproteinase 7; D017239:Paclitaxel