Genetic analysis of drug resistant malignant glioma cells by CHG and microarray
| Project/Area Number |
16591440
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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 | Kobe University |
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Principal Investigator |
KAWAMURA Atsufumi Kobe university, Graduate School of Medicine, Visiting Medical Scientist, 大学院医学系研究科, 医学研究員 (00346256)
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| Co-Investigator(Kenkyū-buntansha) |
KOHMURA Eiji Kobe university, Graduate School of Medicine, Professor, 大学院医学系研究科, 教授 (30225388)
SASAYAMA Takashi Kobe university, University Hospital, Assistant Professor, 医学部附属病院, 助手 (10379399)
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| Project Period (FY) |
2004 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 2006: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2005: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 2004: ¥700,000 (Direct Cost: ¥700,000)
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| Keywords | glioma / etoposide / apoptosis / CGH / マイクロアレイ / cDNA Assay / apoptosis / 分子標的治療 / 薬剤耐性 / 悪性グリオーマ |
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| Research Abstract |
80mg/ml of Etoposide treatment for 1 month formed several colonies in T98G and U251 glioma cells. These cells were not killed in medium containing Etoposide, whereas parent cells were induced to cell death. This result confirmed that this cells was a etoposide resistant glioma cells. Next, we investigated that etoposide resistant glioma cells expressed apoptosis related protein, Smac, Bax, Bcl-2, Bcl-XL, and IAP by western blot, when cells are treated etoposide. In parent cells, pro-apoptotic protein Smac and Bax were up-regulated and anti-apoptotic proteins were down regulated. On the other hand, in etoposide resistant glioma cells, Bcl-2, Bcl-Xl and IAP protein levels were increased by etoposide treatment and Smac and Bax protein levels were unchanged. These results indicate that apoptotic signal was blocked by up-regulation of Bcl-2, Bcl-Xl and IAP at etoposide treatment in etoposide resistant glioma cells.
Specific mTOR inhibitor rapamycin enhances cytotoxicity induced by alkylating
… More
agent 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl-3-nitrosourea (ACNU) in human U251 malignant glioma cells
We investigated the effect of rapamycin on cell growth and death in combination with 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3-nitrosourea (ACNU) in human glioma cells. In U251MG, we confirmed that rapamycin enhanced ACNU-induced apoptosis. We found that rapamysin inhibited ACNU-induced p21 induction, and knocking down of p21 protein by siRNA enhanced ACNU-induced apoptosis in U251MG cells. Furthermore, adenovirus-mediated over-expression of p21 protein rescued U251MG cells from apoptosis induced by ACNU and rapamycin. Finally, treatment of intracerebral U251MG xenografts with a combination of rapamycin and ACNU in vivo resulted in statistically prolonged median survival (p<0.05). These results suggest that rapamycin in combination with DNA-damaging agents may be efficacious in the treatment of malignant gliomas. Trans-4-lodo,4'-boranyl-chalcone induces antitumor activity against malignant glioma cell lines in vitro and in vivo
We studied the antitumor activities of trans-4-lodo,4'-boranyl-chalcone (TLBC), which is a boronic-chalcone derivative, in several glioma cell lines. TLBC showed a dose-dependent inhibition with inhibitory concentration 50% value in the μM range (5.5〜25.5μM) in various glioma cell lines. This cytotoxic effect was the caspase-dependent manner. Also, TLBC lowered levels of anti-apoptotic Bcl-2 and/or Bcl-XL protein in several of the cell lines. In vivo studies showed that in the mice treated with TLBC at 20 mg/kg, mean tumor volume was reduced by 43.9 % (P<0.01) in comparison with the control group. Therefore, we conclude that TLBC may be a potential chemotherapeutic agent for human glioma. Less
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Report
(4 results)
Research Products
(4 results)
