title: MMI-166, a selective matrix metalloproteinase inhibitor, promotes apoptosis in human pancreatic cancer.
abstract: MMI-166 is a third-generation selective matrix metalloproteinase (MMP) inhibitor that prevents tumor invasion and metastasis by downregulating the activity of MMP-2 and MMP-9. However, MMI-166's effect in pancreatic cancer cells has not been widely studied. Initially, we treated SW1990, human pancreatic cancer cells, with 0, 50 or 100 μg/ml of MMI-166 for 24 h. Apoptosis in the cells was then observed by inverted fluorescence microscope and flow cytometry; the apoptosis rate was dependent on MMI-166 concentration. We then injected nude mice with SW1990 cells. Volume of the resulting xenograft tumors in nude mice treated with MMI-166 was far less than that of the control group, whereas their apoptotic index was much greater. Expression of MMP-2, MMP-9, c-myc and survivin were markedly lower in tumors from the treated mice than in the control group. In cell experiments, MMP-2 and MMP-9 activities were downregulated by MMI-166 compared with controls, as were both mRNA and protein levels of MMP-2, MMP-9 and c-myc, although survivin expression did not differ. These results show that MMI-166 can induce apoptosis of pancreatic cancer cells in vitro and in vivo. The mechanism may be related to downregulation of c-myc by MMI-166.
authors.affiliation: Department of General Surgery, Xuanwu Hospital, Capital Medical University, Number 45, Changchun Street, Beijing, 100053, People's Republic of China.
authors.forename: Chong-Chong
authors.initials: CC
authors.lastname: Gao
authors.forename: Ben-Gang
authors.initials: BG
authors.lastname: Gong
authors.forename: Jun-Ben
authors.initials: JB
authors.lastname: Wu
authors.forename: Pi-Guang
authors.initials: PG
authors.lastname: Cheng
authors.forename: Huai-Yong
authors.initials: HY
authors.lastname: Xu
authors.forename: De-Kun
authors.initials: DK
authors.lastname: Song
authors.forename: Fei
authors.initials: F
authors.lastname: Li
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D014408:Biomarkers, Tumor / Q000378:metabolism; D015536:Down-Regulation; D006801:Humans; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D061965:Matrix Metalloproteinase Inhibitors / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D010190:Pancreatic Neoplasms / Q000378:metabolism / Q000473:pathology*; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D013449:Sulfonamides / Q000494:pharmacology*
chemical_list: D014408:Biomarkers, Tumor; C489427:MYC protein, human; D061965:Matrix Metalloproteinase Inhibitors; C419963:N-alpha-(4-(2-phenyl-2H- tetrazole-5-yl) phenyl sulfonyl)-D-tryptophan; D016271:Proto-Oncogene Proteins c-myc; D013449:Sulfonamides; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9