Anti-invasive effect of MMI-166, a new selective matrix metalloproteinase inhibitor, in cervical carcinoma cell lines.
OBJECTIVE
The aim of our study was to evaluate the anti-invasive effect of MMI-166, a new matrix metalloproteinase (MMP) inhibitor in cervical carcinoma cell lines.


METHODS
We analyzed the invasive activities of cervical carcinoma cell lines (CAC-1, CaSki, and SiHa) and the gene expression of various matrix proteinases (matrix metalloproteinase-1 [MMP-1], MMP-2, MMP-9, membrane-type MMP type 1 [MT1-MMP], MT2-MMP, and MT3-MMP) and their inhibitors (tissue inhibitor of metalloproteinase type 1 [TIMP-1] and TIMP-2). The effect of MMI-166 was analyzed by in vitro invasion assay. The cytotoxicity of MMI-166 was determined by MTT assay. The gelatinase activity was analyzed by gelatin zymography.


RESULTS
Cervical carcinoma cell lines, which produced both MMP-2 and MT1-MMP, showed invasive capacity in the in vitro invasion assay. The invasion of cervical carcinoma cells was suppressed by MMI-166. No remarkable suppression of the proliferation by MMI-166 was observed in the MTT assay. Gelatin zymography revealed complete suppression of MMP-2 activity by MMI-166.


CONCLUSIONS
MMI-166 inhibited the MMP-2 activity in cervical carcinoma cells and it is useful for the regulation of cervical carcinoma cell invasion.
Iwasaki
Masahiro
M
Department of Obstetrics and Gynecology, Sapporo Medical University, Sapporo, 060-8543, Japan.
Nishikawa
Akira
A
Fujimoto
Takashi
T
Akutagawa
Noriyuki
N
Manase
Kengo
K
Endo
Toshiaki
T
Yoshida
Koichi
K
Maekawa
Ryuji
R
Yoshioka
Takayuki
T
Kudo
Ryuichi
R
D000230:Adenocarcinoma / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D018093:Gelatinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics; D053517:Matrix Metalloproteinase 15; D053513:Matrix Metalloproteinase 16; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis / Q000235:genetics; D061965:Matrix Metalloproteinase Inhibitors; D020782:Matrix Metalloproteinases / Q000096:biosynthesis / Q000235:genetics; D053504:Matrix Metalloproteinases, Membrane-Associated; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics; D009361:Neoplasm Invasiveness; D013449:Sulfonamides / Q000494:pharmacology*; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000096:biosynthesis / Q000235:genetics; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000096:biosynthesis / Q000235:genetics; D014407:Tumor Cells, Cultured; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics
D004791:Enzyme Inhibitors; D007527:Isoenzymes; C507098:MMP15 protein, human; C507102:MMP16 protein, human; D061965:Matrix Metalloproteinase Inhibitors; C419963:N-alpha-(4-(2-phenyl-2H- tetrazole-5-yl) phenyl sulfonyl)-D-tryptophan; D013449:Sulfonamides; D019715:Tissue Inhibitor of Metalloproteinase-1; D019716:Tissue Inhibitor of Metalloproteinase-2; D018093:Gelatinases; D053517:Matrix Metalloproteinase 15; D053513:Matrix Metalloproteinase 16; D020782:Matrix Metalloproteinases; D053504:Matrix Metalloproteinases, Membrane-Associated; D008666:Metalloendopeptidases; D020778:Matrix Metalloproteinase 2