MMI-166, a selective matrix metalloproteinase inhibitor, promotes apoptosis in human pancreatic cancer

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.