期刊
ONCOLOGY REPORTS
卷 28, 期 5, 页码 1585-1590出版社
SPANDIDOS PUBL LTD
DOI: 10.3892/or.2012.1981
关键词
valproic acid; histone deacetylase inhibitor; MHC class I-related chain molecule; metalloproteinase; osteosarcoma
类别
资金
- Ministry of Education, Culture, Sports, Science and Technology of Japan [23792159]
- Strategic Program Grant for Research Infrastructure Development in Private Institutes
- Hyogo College of Medicine
- Grants-in-Aid for Scientific Research [22591671, 23792159, 23590480] Funding Source: KAKEN
Valproic acid, a histone deacetylase inhibitor, increases the expression of cell surface MHC class I-related chain molecules (MICs) A and B (MICA and B) in osteosarcoma cells and decreases their secretion of soluble MICA and MICB, which are produced by the proteolytic cleavage of cell surface MICs. Osteosarcoma cells have been reported to produce high levels of matrix metalloproteinase (MMP)-2 and -9. In this study, we investigated the involvement of MMP-2 and -9 in the inhibitory action of valproic acid (VPA) on the proteolytic cleavage of cell surface MICs using the U-2 OS and SaOS-2 osteosarcoma cell lines. VPA caused a marked decrease in the expression of MMP-9 mRNA in the U-2 OS and SaOS-2 cells and in the expression of MMP-2 mRNA in the U-2 OS cells, but only a slight decrease in the expression of MMP-2 mRNA in the SaOS-2 cells. The transfection of small interfering RNA (siRNA) for MMP-9 decreased the secretion of soluble MICA and MIC:B by both U-2 OS and SaOS-2 cells, but that of siRNA for MMP-2 did not. The present study therefore demonstrates that the downregulation of MMP-9 mRNA by VPA plays a role in the inhibitory action of VPA on the secretion of soluble MICA and MICB in osteosarcoma cells.
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