2006 Fiscal Year Final Research Report Summary
Study of the inhibitory effects on malignant progression and anticancer drug sensitivity of human squamous cell carcinoma by intensifying cell to cell communication
| Project/Area Number |
17592100
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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 |
Surgical dentistry
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| Research Institution | Health Sciences University of Hokkaido, Institute of Personalized Medical Science |
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Principal Investigator |
NAGAYASU Hiroki Health Sciences University of Hokkaido, Department of Dental Science, Institute of Personalized Medical Science, Associate Professor, 個体差医療科学センター, 准教授 (90265075)
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| Co-Investigator(Kenkyū-buntansha) |
KITAJO Hiroyuki Health Sciences University of Hokkaido, Department of Dental Science, Institute of Personalized Medical Science, Assistant, 個体差医療科学センター, 助教 (00347775)
SHIBATA Toshiyuki Gifu University, School of medicine, Professor, 医学部, 教授 (50226172)
ABIKO Yoshihiro Health Sciences University of Hokkaido, Institute of Personalized Medical Science, Professor, 個体差医療科学センター, 教授 (90260819)
ARISUE Makoto Health Sciences University of Hokkaido, School of dentistry, Professor, 歯学部, 教授 (20091407)
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| Project Period (FY) |
2005 – 2006
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| Keywords | oral cancer / metastasis / invasion / gap junction / anticancer drug |
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| Research Abstract |
Malatolate (Diisoprppyl, 1, 3-dithio1-2-ylidenemalonate, MT) is clinically used as a hepatoprotective agent. Because we noticed that MT induced the differetiation of cultured vascular endothelial cell, we examined the inhibitory effects of MT on invasion of oral squamous cell carcinoma cell (SCC) lines (SAS, Ca9-22, HSC-2,-3,-4) and analyzed its mechanisms of intensifying endothelial and tumor cell to cell adhesion. Five SCC cell lines and rat lung endothelial (RLE) cells were grown in a mixed medium of DMEM and D/F-12 supplemented 10% fetal bovine serum. The invasion capacity of the SCC cells was measured by counting the number of colonies /cm2 formed under the RLE monolayer using a phase contrast microscope. Intercellular junctional communication was examined by the scrape-loading assay. The percentage of cells coupled with the scrape edge was determined by the number of dye-transferred cells. Morphological changes in RLE monolayer observed with electron microscope. Connexin43 expres
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sion of RLE treated with MT was analyzed by western blotting. In an in vitro invasion assay using a RLE monolayer, invasion of tumor cells which had been treated with MT (10ng/ml, 24h) was not affected; however, when had been treated with MT, invasion was significantly inhibited in three cell lines (p<0. 01). Electron-microscopical examination of the RLE monolayer treated with MT showed the development of gap junction like structure. The cell to cell communication increased in RLE monolayers treated with MT(82. 5%), compared to non-treated with MT(32. 5%). A junction associated protein, cnnexin43 was also elevated at RLE and SAS treated with MT. In vivo growth of SAS tumor, primary tumor size was reduced in MT+CDDP treated nude mice compared with CDDP treated nude mice. Conclusion: These findings suggests that MT suppressed tumor cell invasion by intensifying the cell-cell adhesion of vascular endothelium and that enhanced anticancer drug sensitivity by modifying tumor cell communication. Less
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