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: Chong-Chong Gao, Ben-Gang Gong, Jun-Ben Wu, Pi-Guang Cheng, Huai-Yong Xu, De-Kun Song, Fei Li
• Journal: Medical oncology (Northwood, London, England) (Med Oncol) Vol. 32 Issue 1 Pg. 418 (Jan 2015) ISSN: 1559-131X [Electronic] United States
• PMID: 25471789 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers, Tumor
• MYC protein, human
• Matrix Metalloproteinase Inhibitors
• N-alpha-(4-(2-phenyl-2H- tetrazole-5-yl) phenyl sulfonyl)-D-tryptophan
• Proto-Oncogene Proteins c-myc
• Sulfonamides
• MMP2 protein, human
• Matrix Metalloproteinase 2
• MMP9 protein, human
• Matrix Metalloproteinase 9

Topics

• Animals
• Apoptosis (drug effects)
• Biomarkers, Tumor (metabolism)
• Down-Regulation
• Humans
• Male
• Matrix Metalloproteinase 2 (metabolism)
• Matrix Metalloproteinase 9 (metabolism)
• Matrix Metalloproteinase Inhibitors (pharmacology)
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• Pancreatic Neoplasms (metabolism, pathology)
• Proto-Oncogene Proteins c-myc (metabolism)
• Sulfonamides (pharmacology)