Downregulation of matrix metalloproteinase 9 by small interfering RNA inhibits the tumor growth of ovarian epithelial carcinoma in vitro and in vivo.
Matrix metalloproteinase 9 (MMP-9) is upregulated in various types of malignancy, including human ovarian carcinomas. It promotes invasion, metastasis, growth and the survival of malignant cells. However, relatively little is known about the role of MMP9 in epithelial ovarian carcinoma. Therefore, the aim of the present study was to determine the effects of targeting this molecule on ovarian carcinoma progression. A plasmid, psi-MMP-9, carrying a short hairpin RNA against MMP-9 gene expression was constructed and transfected into the human ovarian cancer cell line SKOV3 using a human U6 promoter-driven DNA template approach to determine the effect of MMP-9 gene RNA interference (RNAi) on the proliferation, apoptosis, migration, invasion and tumorigenicity of the human ovarian carcinoma cells. The results demonstrated that siRNA-mediated knockdown of MMP-9 in the human ovarian cancer cell line SKOV3 inhibited cell proliferation, migration and invasion in vitro. The results also demonstrated that downregulation of MMP-9 led to cell apoptosis in SKOV3 cells, inhibited the expression of anti-apoptotic molecules, including B cell lymphoma-2, survivin and X-linked inhibitor of apoptosis protein, and enhanced the activity of capsase-3 and caspase-8. In addition, knockdown of MMP-9 inhibited tumorigenicity in nude mice. Taken together, MMP-9 gene RNAi in ovarian carcinoma cells inhibited proliferation, migration and invasion, induced cell apoptosis in vitro and suppressed tumor growth in nude mice. These results suggest that MMP-9 is an ovarian cancer-associated gene and is a potential target for therapeutic anti-cancer drugs.
Department of Obstetrics and Gynecology, The Second Hospital of Jilin University, Changchun, Jilin 130041, P.R. China.
Fengjun
F
Guo
Department of Urology, The Second Division of The First Hospital, Jilin University, Changchun, Jilin 130031, P.R. China.
Jingyan
J
Tian
Department of Obstetrics and Gynecology, The Second Hospital of Jilin University, Changchun, Jilin 130041, P.R. China.
Manhua
M
Cui
Siping Health School of Jilin Province, Siping, Jilin 136000, P.R. China.
Meiru
M
Fang
Department of Obstetrics and Gynecology, The Second Hospital of Jilin University, Changchun, Jilin 130041, P.R. China.
Lin
L
Yang
D000818:Animals; D017209:Apoptosis / Q000235:genetics; D063646:Carcinogenesis / Q000235:genetics*; D000077216:Carcinoma, Ovarian Epithelial; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006801:Humans; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis / Q000235:genetics*; D051379:Mice; D009361:Neoplasm Invasiveness / Q000235:genetics; D009375:Neoplasms, Glandular and Epithelial / Q000235:genetics* / Q000473:pathology; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000473:pathology; D034741:RNA, Small Interfering / Q000235:genetics; D023041:Xenograft Model Antitumor Assays
D034741:RNA, Small Interfering; D020780:Matrix Metalloproteinase 9