2000 Fiscal Year Final Research Report Summary
MMP inhibitor BPHA inhibit the potential of tumor growth and metastasis in human lung cancer cell lin
| Project/Area Number |
11671328
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Thoracic surgery
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| Research Institution | The university of Tokushima |
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Principal Investigator |
KONDO Kazuya School of Medicine, The University of Tokushima, Assistant Professor, 医学部, 講師 (10263815)
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| Co-Investigator(Kenkyū-buntansha) |
SAKIYAMA Syouji School of Medicine, The University of Tokushima Assistant, 医学部, 助手 (60291986)
KOMAKI Kansei Medical School Hospital, The University of Tokushima, Assistant Professor, 医学部・附属病院, 講師 (60215382)
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| Project Period (FY) |
1999 – 2000
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| Keywords | MMP inhibitor / lung cancer / tumor invasion / BPHA / MM1-166 / Haptoinvasion assay |
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| Research Abstract |
A newly developed matrix metalloproteinase (MMP) inhibitor, N-biphenyl sulfonylphenylalanine hydroxiamic acid (BPHA)(Shionogi Co.) potently which inhibits MMP-2, -9, and -14 but not MMP-1, -3, or, -7, and MMI-166 (Shionogi Co.) which inhibits MMP-2, and -9 selectively. We examined the inhibition of in vitro invasion potential of lung cancer cell line Ma10 and fibrosarcoma cell line HT-1080 by BPHA and MMI-166 using in vitro haptoinvasion assay. HT-1080 cell line had the gelatinolytic activity of MMP-9 and MMP-2 using gelatin zymography. On the other hand, Ma10 cell line had the gelatinolytic activity of MMP-2 but not MMP-9.Although BPHA did not inhibit the potential of migration for HT-1080 and Ma10, it inhibit the potential of in vitro invasion for HT-1080 (63%) and Ma10 (41%). MMI-166 (16 uM) inhibit the potential of in vitro invasion for HT-1080 (83.4%) and Ma10 (52.7%). Moreover, We exminated the inhibition of tumor growth and lymph nodes metastasis of Ma10 cell line by MMI-166 using subcutaneous implantation model and lymphogenous metastatic model. The oral administration of MMI-166 (100-300mg/kg body) to SCID mice had no side effect. The concentration of 200mg/kg body MMI-166 inhibited the tumor growth in subcutaneous model, and slightly inhibited lymphogenous metastasis to the mediastinum in lymphogenous metastatic model. These results indicate that selective MMP inhibitors inhibit not only angiogenesis but also tumor invasion.
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