[Inhibitory effects of matrix metalloproteinase (MMP) inhibitor LY52 on expression of MMP-2 and MMP-9 and invasive ability of human ovarian carcinoma cell line SKOV3].
OBJECTIVE
Enhanced expression and activation of matrix metalloproteinase-2 (MMP-2) and MMP-9 are associated with tumor progression, invasion, and metastasis. Using synthetic MMP inhibitors to block the proteolytic activity of these enzymes is a potential strategy of treating cancer. This study was to observe the inhibitory effects of LY52, a synthetic specific MMP inhibitor, on the expression of MMP-2 and MMP-9 and invasive ability of human ovarian carcinoma cell line SKOV3.


METHODS
The inhibitory effect of LY52 on growth of SKOV3 cells was measured by MTT and clonogenic assays. The inhibitory effect of LY52 on the activity of gelatin was evaluated by spectrophotometry using succinylated gelatin as substrate. The inhibitory effect of LY52 on the expression of MMP-2 and MMP-9 was analyzed using SDS-PAGE zymography. The adhesive ability of SKOV3 cells to fibronectin (FN), laminin (LN), and matrigel was measured using MTT assay. The invasive ability of SKOV3 cells was assessed with a transwell cell culture chamber.


RESULTS
LY52 had weak cytostatic effect on SKOV3 cells, the inhibitory rates were 10.54%-37.66% within 120 h incubation when the concentration was 10 microg/ml. LY52 inhibited gelatin degradation via suppressing the activities of gelatinases, the 50% inhibitory concentration (IC50) was 11.9 microg/ml. When treated with 0.1, 1, 10, 100, or 1,000 microg/ml LY52 for 24 h, the expression of MMP-2 in SKOV3 cells was suppressed by 10.66%-31.47%, and the expression of MMP-9 was suppressed by 22.56%-56.71%. When treated with LY52 for 1 h, the maximum inhibitory rates of adhesion of SKOV3 cells to FN, LN, and matrigel were 29.79%, 48.94%, and 50.92%, respectively. When treated with 0.1, 1, 10, 100, and 1,000 microg/ml LY52 for 24 h, the inhibitory rates of invasion of SKOV3 cells were 7.5%, 42.07%, 66.54%, 72.15%, and 82.84%, respectively.


CONCLUSIONS
LY52 suppresses the invasion of SKOV3 cells via inhibiting the expression of MMP-2 and MMP-9.
Yuan
Yun-Xia
YX
Department of Pharmacology, Faculty of Pharmacy, Shandong University, Jinan, Shandong, 250012, P. R. China.
Xu
Wen-Fang
WF
Liu
Jian
J
Chen
Ming-Hui
MH
Meng
Hong
H
Qu
Xian-Jun
XJ
D002109:Caffeic Acids / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D061965:Matrix Metalloproteinase Inhibitors; D009361:Neoplasm Invasiveness; D010051:Ovarian Neoplasms / Q000378:metabolism / Q000473:pathology*; D011392:Proline / Q000031:analogs & derivatives* / Q000494:pharmacology
D002109:Caffeic Acids; C515003:LY52 compound; D061965:Matrix Metalloproteinase Inhibitors; D011392:Proline; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9