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2005 Fiscal Year Final Research Report Summary

Radiation sensitization of cancer cells by RNA interference

Research Project

Project/Area Number 16591220
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Radiation science
Research InstitutionNara Medical University School of Medicine

Principal Investigator

OHNISHI Ken  Nara Medical University, Department of Biology, Associate Professor, 医学部, 助教授 (50152195)

Project Period (FY) 2004 – 2005
KeywordsNBS1 / XIAP / NF-κB / siRNA / radiation / DNA-repair / cell survival / sensitization
Research Abstract

NBS 1 is essential for the repair of radiation induced DNA double-strand breaks (DSBs) in yeast and higher vertebrate cells. In this paper, we examined whether suppressed NBS1 expression by small interference RNA (siRNA) could enhance radiation sensitivity in cancer cells with different p53 status. We used human non-small cell lung cancer cells, differing in p53 gene status (H1299/wtp53 cells bearing wild-type p53 or H1299/mp53 cells bearing mutant p53). A DNA cassette expressing siRNA targeted for the NBS1 gene was transfected into those cell lines and radiation sensitivity was examined with a colony-forming assay. Cellular levels of NBS1 and other proteins were analyzed using Western blot. We found that the radiation sensitivity of H1299/wtp53 and H1299/mp53 cells was enhanced by transfection of the DNA cassette. In the NBS1-siRNA transfected cells, we observed decreased constitutive expression of NBS1 protein and decreased radiation-induced accumulation of phosphorylated NBS1 protein. In addition, radiation-induced expression of the transcription factor NF-κB and XIAP (X-chromosome-linked inhibitor of apoptosis protein) was suppressed by NBS1-siRNA. Enhanced X-ray, sensitivity, after NBS1-siRNA transfection, was achieved in p53 wild-type and even more pronounced in p53 mutant cells. The transfection of siRNA targeted for XIAP also enhanced X-ray sensitivity even more pronounced for p53 mutant cells compared to p53 wild-type cells. Our data suggest that the sensitization to radiation is a result of NBS1-siRNA-mediated suppression of X-ray-induced cell-survival signaling pathways via NF-κB and XIAP and that it is a novel radiation therapy-sensitizing agent, particularly in human p53 mutant cancer cells.

  • Research Products

    (31 results)

All 2006 2005 2004 Other

All Journal Article (31 results)

  • [Journal Article] Heat-induced phosphorylation of NBS1 in human skin fibroblast cells.2006

    • Author(s)
      Ohnishi K., et al.
    • Journal Title

      J.Cell.Biochem. (in press)

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] LY294002, an inhibitor of PI-3K, enhances heat sensitivity independently of p53 status in human lung cancer cells.2006

    • Author(s)
      Ohnishi K., et al.
    • Journal Title

      Int.J.Oncol. (in press)

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] 変異型p53タンパク質に正常機能を回復させるシャペロン分子2006

    • Author(s)
      大西健 他
    • Journal Title

      放射線生物研究 41

      Pages: 99-108

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] LY294002, an inhibitor of PI-3K, enhances heat sensitivity independently of p53 status in human lung cancer cells.2006

    • Author(s)
      Ohnishi K., Yasumoto J.-I., Takahashi A., Ohnishi T.
    • Journal Title

      Int.J.Oncol. (in press)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Apoptosis induced by high-LET radiations is not affected by cellular p53 gene status.2005

    • Author(s)
      Takahashi A. et al.
    • Journal Title

      J.Radiat.Biol. 81

      Pages: 581-586

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Combination of the antivascular agent ZD6126 with hypoxic cytotoxin treatment, with reference to the effect on quiescent tumor cells and the dependency on p53 status of tumor cells.2005

    • Author(s)
      Masunaga S, et al.
    • Journal Title

      Oncol.Rep. 14

      Pages: 393-400

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Glycerol enhances radiosensitivity in a human oral squamous cell carcinoma cell line (Ca9-22) bearing a mutant p53 gene via Bax-mediated induction of apoptosis.2005

    • Author(s)
      Imai Y., et al.
    • Journal Title

      Oral Oncol. 41

      Pages: 631-636

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Glycerol enhances radiosensitivity in a human oral squamous cell carcinoma cell line (Ca9-22) bearing a mutant p53 gene via Bax-mediated induction of apoptosis.2005

    • Author(s)
      Imai Y., Ohnishi K., Yasumoto J.-I., Kajiwara A., Yamakawa N., Takahashi A., Ohnishi T., Kirita T.
    • Journal Title

      Oral Oncology 41

      Pages: 631-636

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Combination of the antivascular agent ZD6126 with hypoxic cytotoxin treatment, with reference to the effect on quiescent tumor cells and the dependency on p53 status of rumor cells.2005

    • Author(s)
      Masunaga S., Nagasawa H., Uto Y., Hori H., Ohnishi K., Takahashi A., Ohnishi T., Suzuki M., Nagata K., Kinashi Y., Ono K.
    • Journal Title

      Oncology Reports 14

      Pages: 393-400

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Apoptosis induced by high-LET radiations is not affected by cellular p53 gene status.2005

    • Author(s)
      Takahashi A., Matsumoto H., Furusawa Y., Ohnishi K., Ishioka N., Ohnishi T.
    • Journal Title

      International Journal of Radiation Biology 81

      Pages: 581-586

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Evidence for the involvement of double-strand breaks in heat-induced cell killing.2004

    • Author(s)
      Takahashi A., et al.
    • Journal Title

      Cancer Res. 64

      Pages: 8839-8845

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Sensitization by glycerol for CDDP-therapy against human cultured cancer cells and tumors bearing mutated p53 gene.2004

    • Author(s)
      Yuki K, et al.
    • Journal Title

      Apotosis 9

      Pages: 853-859

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Effects of a heat shock protein inhibitor KNK437 on heat sensitivity and heat tolerance in human squamous cell carcinoma cell lines differing in p53 status.2004

    • Author(s)
      Ohnishi K., et al.
    • Journal Title

      Int.J.Radiat.Biol. 80

      Pages: 607-614

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] High-LET radiation enhanced apoptosis but not necrosis regardless of p53 status.2004

    • Author(s)
      Takahashi A, et al.
    • Journal Title

      Int.J.Radiat.Oncol.Biol.Phys. 60

      Pages: 591-597

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Effect of mild temperature hyperthermia and p53 status on the size of hypoxic fractions in sold tumors, with reference to the effect in intratumor quiescent cell populations.2004

    • Author(s)
      Masunaga S., et al.
    • Journal Title

      Int.J.Radiat.Oncol.Biol.Phys. 60

      Pages: 570-577

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] C-terminal peptides of p53 molecules enhance radiation-induced apoptosis in human mutant p53 cancer cells.2004

    • Author(s)
      Ohnishi K., et al.
    • Journal Title

      Apotosis 9

      Pages: 597-597

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Glycerol enhances CDDP-induced growth inhibition of thyroid anaplastic carcinoma tumor carrying mp53 gene.2004

    • Author(s)
      Yuki K., et al.
    • Journal Title

      Oncol.Rep. 11

      Pages: 821-824

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Apoptosis-related gene expression after hyperthermia in human tongue squamous cell carcinoma cells harboring wild-type or mutated p53.2004

    • Author(s)
      Yasumoto J., et al.
    • Journal Title

      Cancer Lett. 204

      Pages: 41-51

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Radiation-induced apoptosis in SCID mouse spleen after low dose or low dose-rate irradiation.2004

    • Author(s)
      Takahashi A., et al.
    • Journal Title

      Int.J.Low Radiat. 1

      Pages: 199-207

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Hyperthermic cancer therapy combined with inhibitors targeted against heat-induced signaling factors.2004

    • Author(s)
      Ohnishi K. et al.
    • Journal Title

      Japan.J.Hyperthermic Oncol. 20

      Pages: 143-159

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Radiation-induced apoptosis in SCID mouse spleen after low dose or low dose-rate irradiation.2004

    • Author(s)
      Takahashi A., Ohnishi K., Ohnishi T.
    • Journal Title

      International Journal of Low Radiation 1

      Pages: 199-207

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Apoptosis-related gene expression after hyperthermia in human tongue squamous cell carcinoma cells harboring wild-type or mutated p53.2004

    • Author(s)
      Yasumoto J., Kirita T., Takahashi A., Ohnishi K., Imai Y., Yuki K., Ohnishi T.
    • Journal Title

      Cancer Letter 204

      Pages: 41-51

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Glycerol enhances CDDP-induced growth inhibition of thyroid anaplastic carcinoma tumor carrying mp53 gene.2004

    • Author(s)
      Yuki K., Takahashi A., Ota I., Ohnishi K., Yasumoto J.-i, Kanata H., Yane K., Hosoi H., Ohnishi T.
    • Journal Title

      Oncology Reports 11

      Pages: 821-824

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] C-terminal peptides of p53 molecules enhance radiation-induced apoptosis in human mutant p53 cancer cells.2004

    • Author(s)
      Ohnishi K., Takahashi A., Inaba H., Yasumoto J., Yuki K., Ohnishi T.
    • Journal Title

      Apotosis 9

      Pages: 591-597

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Effect of mild temperature hyperthermia and p53 status on the size of hypoxic fractions in sold tumors, with reference to the effect in intratumor quiescent cell populations.2004

    • Author(s)
      Masunaga S., Takahashi A., Ohnishi K., Ohnishi T., Nagata K., Suzuki M., Kinashi Y., Ono K.
    • Journal Title

      International Journal of Radiation Oncology Biology Physics 60

      Pages: 570-577

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] High-LET radiation enhanced apoptosis but not necrosis regardless of p53 status2004

    • Author(s)
      Takahashi A, Matsumoto H, Yuki K, Yasumoto J, Kajihara A, Aoki M, Furusawa Y, Ohnishi K, Ohnishi T.
    • Journal Title

      International Journal of Radiation Oncology Biology Physics 60

      Pages: 591-597

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Effects of a heat shock protein inhibitor KNK437 on heat sensitivity and heat tolerance in human squamous cell carcinoma cell lines differing in p53 status.2004

    • Author(s)
      Ohnishi K., Takahashi A., Yokota S., Ohnishi T.
    • Journal Title

      International Journal of Radiation Biology 80

      Pages: 607-614

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Sensitization by glycerol for CDDP-therapy against human cultured cancer cells and tumors bearing mutated p53 gene.2004

    • Author(s)
      Yuki K., Takahashi A., Ota I., Ohnishi K., Yasumoto J., Yane K., Kanata H., Hosoi H., Ohnishi T.
    • Journal Title

      Apotosis 9

      Pages: 853-859

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Evidence for the involvement of double-stand breaks in heat-induced cell killing.2004

    • Author(s)
      Takahashi A., Matsumoto H., Nagayama K., Kitano M., Hirose S., Tanaka H., Mori E., Yamakawa N., Yasumoto J., Yuki K., Ohnishi K., Ohnishi T.
    • Journal Title

      Cancer Research 64

      Pages: 8839-8845

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] DNA修復関連遺伝子を標的としたRNA干渉によるがん細胞の放射線増感

    • Author(s)
      大西健 他
    • Journal Title

      癌の臨床 (印刷中)

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Heat-induced phosphorylation of NBS1 in human skin fibroblast cells.

    • Author(s)
      Ohnishi K., Scuric Z., Yau D., Schiestl R.H., Okamoto N., Takahashi A., Ohnishi T.
    • Journal Title

      J.Cell.Biochem. (in press)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2007-12-13  

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