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

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• 作者：Chong-chong Gao (1)
  Ben-gang Gong (2)
  Jun-ben Wu (2)
  Pi-guang Cheng (2)
  Huai-yong Xu (2)
  De-kun Song (2)
  Fei Li (1)
  
• 关键词：Pancreatic cancer ; MMI ; 166 ; MMP inhibitor ; c ; myc ; Apoptosis ; SW1990 cell
• 刊名：Medical Oncology
• 出版年：2015
• 出版时间：January 2015
• 年：2015
• 卷：32
• 期：1
• 全文大小：1,938 KB
• 参考文献：1. Maekawa R, Maki H, Wada T, Yoshida H, Nishida-Nishimoto K, Okamoto H, et al. Anti-metastatic efficacy and safety of MMI-166, a selective matrix metalloproteinase inhibitor. Clin Exp Metastasis. 2000;18(1):61-. CrossRef
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  3. Fujino H, Kondo K, Ishikura H, Maki H, Kinoshita H, Miyoshi T, et al. Matrix metalloproteinase inhibitor MMI-166 inhibits lymphogenous metastasis in an orthotopically implanted model of lung cancer. Mol Cancer Ther. 2005;4(9):1409-6. CrossRef
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  13. Maki H, Hojo K, Tanaka H, Sawada TY, Maekawa R, Yoshioka T, et al. Augmented anti-metastatic efficacy of a selective matrix metalloproteinase inhibitor, MMI-166, in combination with CPT-11. Clin Exp Metastasis. 2002;19(6):519-6. CrossRef
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• 作者单位：Chong-chong Gao (1)
  Ben-gang Gong (2)
  Jun-ben Wu (2)
  Pi-guang Cheng (2)
  Huai-yong Xu (2)
  De-kun Song (2)
  Fei Li (1)
  
  1. Department of General Surgery, Xuanwu Hospital, Capital Medical University, Number 45, Changchun Street, Beijing, 100053, People’s Republic of China
  2. Department of Hepatobiliary Surgery, Binzhou People’s Hospital, Binzhou Medical College, Shandong, 256600, People’s Republic of China
  
• ISSN：1559-131X

文摘

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.