2002 Fiscal Year Final Research Report Summary
Regulation of cell cycle progression by ganglioside-a novel strategy against malignant glioma
| Project/Area Number |
13671434
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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 |
Cerebral neurosurgery
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| Research Institution | Osaka University |
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Principal Investigator |
IZUMOTO Shuichi Osaka University Graduate School of Medicine, Assistant Professor, 医学系研究科, 助手 (40324769)
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| Co-Investigator(Kenkyū-buntansha) |
NAKATSUJI Yuji Osaka University Graduate School of Medicine, Assistant Professor, 医学系研究科, 助手 (20332744)
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| Project Period (FY) |
2001 – 2002
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| Keywords | Ganglioside / GM3 / glycolipid / glioma / brain tumor / malignant glioma / apotosis |
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| Research Abstract |
To investigate whether gangliosides modulate the progression of glioma cells, GM3, the simplest ganglioside, was administered into the culture of glioma cells and into the glioma-bearing rats via the cistema magna. (1) Four primary glioma cells and 4 glioma cell lines were cultured with GM3. MTT assay demonstrated that the glioma pells were inhibited those proliferation by GM3 with the concentration of 20 to 200 micromole(P<0.05). The inhibition was dependent on the concentration of GM3. (2) Rat glioma model for the in vivo analysis was made by the inoculation of C6 glioma cells into the rat meningeal space. Treated rats (n=20), those were administered GM3 on 10 days after glioma-cell-inoculation, survived 22.0 days, whereas the control rats(n=15) survived 19.5 days(P<0.05). Acute toxicity was not detected on the rats after GM3 administration. (3) On the pathological examination by TUNEL method,GM3 was found to induce apoptosis on the glioma cells. The apoptotic cells were detected from 1 to 3 days after administration of GM3 in the rat brain and detected only on the surface of the mass of glioma cells. Those results demonstrated that GM3 does not infiltrate well into the brain or into the mass of glioma cells.
To investigate whether GM3 interfere with the invasion of the glioma cells, Boyden chamber assay and invasion assay with slice culture model were performed.(4) As a result, glioma cells were inhibited its motility and invasion by GM3, that was dependent on the concentration of GM3.
These results demonstrate that GM3 inhibits both the proliferation and invasion of glioma cells. The local administration of GM3 as a new strategy for the control of glioma may be a useful and safe method.
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