Effect of a phosphatidylinositol 3-kinase inhibitor wortmannin on radiation and bleomycin sensitivities.

磷脂酰肌醇 3-激酶抑制剂渥曼青霉素对辐射和博莱霉素敏感性的影响。

基本信息

  • 批准号:
    09670911
  • 负责人:
  • 金额:
    $ 0.83万
  • 依托单位:
  • 依托单位国家:
    日本
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
  • 财政年份:
    1997
  • 资助国家:
    日本
  • 起止时间:
    1997 至 1998
  • 项目状态:
    已结题

项目摘要

ATM and DNA-dependent protein kinase catalytic subunit (DNA-PKcs) have been shown to have sequences homologous to the catalytic domains of mammalian phosphatidylinositol 3-kinase (PI3-kinase). In order to determine the contribution of ATM and DNA-PKcs to the increased sensitivity of cells to DNA-damaging agents observed in the presence of PI3-kinase inhibitors, we examined the effects of a PI3-kinase inhibitor, wortmannin, on cellular sensitivity to belomycin (BLM), mitomycin C (MMC), X-irradiation and ultraviolet (UV9-irradiation using2 human tumor cell lines (T98G and A172), a human fibroblast cell line (LM2 17), an ataxia telangiectasia (AT) cell line (AT3BISV), a scid murine cell line (SCF) and control murine cell line (CBF). Wortmannin sensitized all of the cells, including AT3BISV and SCF, to BLM and X-irradiation, but not to MMC or UV-irradiation. Hypersensitivity to BLM and X-irradiation and normal sensitivity to MMC and UV-irradiation are characteristic phenotypes of both AT and scid mice. DNA-dependent protein kinase (DNA-PK) activity was suppressed by wortmannin to 45-65% of the control values in all of the cells except SCF, in which DNA-PK activity was not detected. Wortmannin also induced radioresistant DNA synthesis, which is a cellular phenotype of AT, in T98Gand SCF cells, but did not change the DNA synthesis rates after X-irradiation in AT3BISV.Our data Suggest that wortmannin decreases the activities of both the ATM protein and DNA-PK, indicating that it might be of use as a sensitizing agent for radiotherapy and chemotherapy.
ATM和dna依赖性蛋白激酶催化亚基(DNA-PKcs)已被证明具有与哺乳动物磷脂酰肌醇3-激酶(pi3 -激酶)催化结构域同源的序列。为了确定ATM和DNA-PKcs对存在pi3激酶抑制剂的细胞对dna损伤剂的敏感性增加的贡献,我们使用2种人肿瘤细胞系(T98G和A172)、人成纤维细胞系(LM2 17)、失联毛细血管扩张细胞系(AT3BISV)检测了pi3激酶抑制剂wortmannin对贝洛霉素(BLM)、丝裂霉素C (MMC)、x射线照射和紫外线(uv9)照射的细胞敏感性的影响。小鼠细胞系(SCF)和对照小鼠细胞系(CBF)。Wortmannin使包括AT3BISV和SCF在内的所有细胞对BLM和x射线照射敏感,但对MMC或uv照射不敏感。AT和scid小鼠对BLM和x照射超敏,对MMC和uv照射正常敏感。除SCF细胞外,wortmannin将dna依赖性蛋白激酶(DNA-PK)活性抑制至对照组的45-65%。SCF细胞中DNA-PK活性未检测到。Wortmannin还在t98gv和SCF细胞中诱导了抗辐射DNA合成,这是AT的一种细胞表型,但在AT3BISV中,x射线照射后DNA合成率没有改变。我们的数据表明,wortmannin降低了ATM蛋白和DNA-PK的活性,表明它可能用作放疗和化疗的增敏剂。

项目成果

期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Hosoi Yoshio: "Effect of combination treatment of 15 cGy total body irradiation and OK-432 on spontaneous lung metastasis and mitogenic response of splenocyte in mice." Radiation Oncology Investigations. 5. 283-288 (1997)
Hosoi Yoshio:“15 cGy 全身照射和 OK-432 联合治疗对小鼠自发性肺转移和脾细胞有丝分裂反应的影响。”
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    0
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Sakamoto Kiyohiko: "Fundamental and clinical studies on cancer control with total or upper half body irradiation." J.Jpn.Society for Therapeutic Radiology & Oncology. 9. 161-175 (1997)
坂本清彦:“通过全身或上半身照射控制癌症的基础和临床研究。”
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    0
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Takai Yoshihiro: "Single dose radiocurability of four murine solid tumors and predictive assay for the curability in situ." Journal of Radiation Research. 38. 233-240 (1997)
Takai Yoshihiro:“四种小鼠实体瘤的单剂量放射治愈性以及原位治愈性的预测测定。”
  • DOI:
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  • 影响因子:
    0
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Yoshio Hosoi: "A phosphatidylinositol 3-kinase inhibitor wortmannin induces radioresistant DNA synthesis and sensitizes cells to bleomycin and ionizing radiation" International Journal of Cancer. 78. 642-647 (1998)
Yoshio Hosoi:“磷脂酰肌醇 3-激酶抑制剂渥曼青霉素诱导抗辐射 DNA 合成并使细胞对博来霉素和电离辐射敏感”《国际癌症杂志》。
  • DOI:
  • 发表时间:
  • 期刊:
  • 影响因子:
    0
  • 作者:
  • 通讯作者:
Yoshio Hosoi: "A phosphatidylinositol 3-kinase inhibitor wortmannin induces radioresistant DNA synthesis and sensitizes cells to bleomycin and ionizing radiation." International Journal of Cancer. 78. 642-647 (1998)
Yoshio Hosoi:“磷脂酰肌醇 3-激酶抑制剂渥曼青霉素可诱导抗辐射 DNA 合成并使细胞对博莱霉素和电离辐射敏感。”
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    0
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HOSOI Yoshio其他文献

HOSOI Yoshio的其他文献

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{{ truncateString('HOSOI Yoshio', 18)}}的其他基金

Radiosensitization of radioresistant cancer stem cells by inhibition of ATM
通过抑制 ATM 实现抗辐射癌症干细胞的放射增敏
  • 批准号:
    23659588
  • 财政年份:
    2011
  • 资助金额:
    $ 0.83万
  • 项目类别:
    Grant-in-Aid for Challenging Exploratory Research
Radiation sensitization though regulation of transcriptional factor Sp1
通过转录因子 Sp1 的调节实现放射增敏
  • 批准号:
    18390330
  • 财政年份:
    2006
  • 资助金额:
    $ 0.83万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
Inhibition of DNA-PK activity and radio-sensitization induced by single strand DNA
单链 DNA 诱导的 DNA-PK 活性抑制和放射增敏作用
  • 批准号:
    15390357
  • 财政年份:
    2003
  • 资助金额:
    $ 0.83万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
Inhibition of DNA-PK activity by phosphorothioate oligonucleotides
硫代磷酸酯寡核苷酸对 DNA-PK 活性的抑制
  • 批准号:
    12470184
  • 财政年份:
    2000
  • 资助金额:
    $ 0.83万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)

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