Matrix metalloproteinase inhibitor MMI-166 inhibits lymphogenous metastasis in an orthotopically implanted model of lung cancer
| Autor: | Taeko Nagao, Haruhiko Fujino, Hisashi Ishikura, Yasumasa Monden, Hideo Maki, Yuji Takahashi, Hiromitsu Takizawa, Kazuya Kondo, Naruhiko Sawada, Hidetaka Kinoshita, Takanori Miyoshi, Shoji Sakiyama |
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| Rok vydání: | 2005 |
| Předmět: |
Male
Cancer Research Lung Neoplasms Matrix metalloproteinase inhibitor Injections Subcutaneous Mice SCID Matrix Metalloproteinase Inhibitors Matrix metalloproteinase Metastasis Mice In vivo Carcinoma Non-Small-Cell Lung Tumor Cells Cultured medicine Carcinoma Animals Humans Neoplasm Invasiveness Lung cancer Survival rate Sulfonamides Neovascularization Pathologic business.industry medicine.disease Survival Rate Disease Models Animal Oncology Lymphatic Metastasis Mediastinal lymph node Immunology Cancer research business |
| Zdroj: | Molecular Cancer Therapeutics. 4:1409-1416 |
| ISSN: | 1538-8514 1535-7163 |
| DOI: | 10.1158/1535-7163.mct-05-0031 |
| Popis: | Matrix metalloproteinases (MMP) are considered to be critically involved in tumor invasion and the metastasis of various cancers. MMI-166 is a selective inhibitor of matrix metalloproteinase (MMP-2, MMP-9, and MMP-14). The purpose of this study was to evaluate the effects of MMI-166 on both the growth of the implanted tumor and the lymph node metastasis of the mediastinum and prolonging the life span, using an orthotopic implantation model of the Ma44-3 cancer cell line. We examined the anti-invasive effect of MMI-166 in lung cancer cell lines using an in vitro invasion assay. Next, we examined the anticancer effect of MMI-166 in vivo. MMI-166 (200 mg/kg body weight) or a vehicle was administered orally to the orthotopically implanted lung cancer model. MMI-166 dose-dependently inhibited the invasion of cancer cell lines with expressions of MMP-2 and/or MMP-9 in vitro. In vivo, MMI-166 significantly inhibited mediastinal lymph node metastasis in this orthotopic model (weight of the mediastinum: control, 0.089 ± 0.009 versus MMI-166, 0.069 ± 0.008 mg; P = 0.005; metastatic area: control, 93,495 ± 55,747 versus MMI-166, 22,747 ± 17,478 pixels; P = 0.045). MMI-166 prolonged the life span by 6 days in median survival time in the orthotopically implanted model (P = 0.039). These results showed that MMI-166 could possibly inhibit lymph node metastasis and prolong the life span in lung cancer patients. |
| Databáze: | OpenAIRE |
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