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A research of regulation of glycosphingolipids gene expression and anticancer drug sensitivity in human oral cancer cell lines

Research Project

Project/Area Number 16591879
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Pathobiological dentistry/Dental radiology
Research InstitutionHokkaido University

Principal Investigator

KANEKO Masanori  Hokkaido University, Graduate School of Dental Medicine, Instructor, 大学院歯学研究科, 助手 (10214470)

Co-Investigator(Kenkyū-buntansha) INOKUCHI Jinichi  Hokkaido University, Graduate School of Pharmaceutical Sciences, Asso. Prof., 大学院薬学研究科, 助教授 (70131810)
Project Period (FY) 2004 – 2005
Project Status Completed (Fiscal Year 2005)
Budget Amount *help
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2005: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2004: ¥2,200,000 (Direct Cost: ¥2,200,000)
Keywordsglycosphingolipids / ganglioside / GM3 / oral squamous cell carcinoma / anti-cancer drug sensitivity / SAT-1 gene / cisplatin / inhibitor of glucosylceramide synthase / ガングリオシド合成阻害剤 / 抗癌剤抵抗性
Research Abstract

To clarify the relation between the amount of ganglioside GM3 on the surface of the cell membrane and the anti-cancer drug sensitivity, this research was done with 14 human oral squamous cell carcinoma cell lines which were obtained from JCRB (Ca9-22,HSC-2,HSC-3,HSC-4,Ho-1-N-1,Ho-1-U-1,KON, KOSC2-c13,SAT, SAS, SCC-4,SKN-3,OSC-19,OSC-20). The ganglioside contents were detected by thin layer chromatography for the cell lines. The expression of GM3 synthesis enzyme (SAT-1) gene of each cell line was measured by the Real time PCR. A quantitative difference was seen by the cell lines as for the amount of GM3 and the SAT-1 expression. The 50% effective doses (Ic50) of cisplatin were calculated from the dose-response curves which were derived from MTT assay. The Ic50 of the cisplatin showed positive correlation with SAT-1 expression (R=0.717) in 14 cell lines. Next, the cisplatin sensitivity was examined after controlling the expression of GM3 in the cell line Ca9-22. The Ca9-22 cell line was selected to transfect SAT-1 gene, because it has rich LacCer which is the precursor of GM3 and little amount of GM3. However, the SAT-1 transfected clone did not increase GM3 than a wild type, but GM2 which was made of GM3 had increased. The difference of the cisplatin sensitivity was not seen between the SAT-1 gene transfected clone and a wild type. Inhibitors of glucosylceramide synthase, such as D-PDMP, PBPP and P4 were used to detect the role of ganglioside on Ca9-22, 0SC-20 and SCC-4 cell lines, which showed no definite effect on sensitivity of cisplatin and etoposide. It was suspected that GM3 alone do not have a relation with the cisplatin sensitivity, and more factors may take part in. Further investigation should be done to detect the mechanism of ganglioside on the cell signaling which induce apoptosis by anti-cancer drug.

Report

(3 results)
  • 2005 Annual Research Report   Final Research Report Summary
  • 2004 Annual Research Report

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Published: 2004-04-01   Modified: 2016-04-21  

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