Abstract
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.
Highlights
Ovarian epithelial carcinoma, which accounts for 90% of cases of ovarian cancer, continues to be the leading cause of mortality and has the highest mortality rate among gynecological malignancies worldwide [1]
In RT‐qPCR results demonstrated that no significant inhibition of brief, 2x105 SKOV3 cells in RPMI‐1640 medium containing Matrix metalloproteinases (MMPs)‐9 mRNA expression was observed in the control group
Compared with the psi‐NC group and control pore polycarbonate coated with 1 mg/ml Matrigel; the lower group, Matrix metalloproteinase 9 (MMP‐9) mRNA expression in the psi‐MMP‐9 group was chamber was filled with RPMI‐1640 media containing 10% significantly decreased (Fig. 1A; P
Summary
Ovarian epithelial carcinoma, which accounts for 90% of cases of ovarian cancer, continues to be the leading cause of mortality and has the highest mortality rate among gynecological malignancies worldwide [1]. Despite the improved combination of surgery, radiation and chemotherapy, the 5‐year survival rates of ovarian cancer patients remain poor due to the difficulty in removing the highly invasive ovarian tumor and the short‐ and long‐term adverse effects of conventional post‐surgical adjuvant therapies [2,3]. The development of new therapeutics or drugs to combat this disease is essential to improve the survival rate of patients with ovarian epithelial carcinoma. Tumor cells acquire invasive and metastatic characteristics mainly due to their ability to produce and activate proteolytic enzymes, including serine, metallo‐ and cysteine proteases, which are able to degrade extracellular matrix (ECM) components and break down natural barriers, thereby aiding tumor invasion and metastasis [4]. It has been reported that MMPs are able to degrade ECM and basal membrane components [5,6] and are
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