Silencing Ku80 using small interfering RNA enhanced radiation sensitivity in vitro and in vivo

Yoshinori Nimura, Tetsuya Kawata, Katsuhiro Uzawa, Junko Okamura, Cuihua Liu, Masayoshi Saito, Hideaki Shimada, Naohiko Seki, Akira Nakagawara, Hisao Ito, Takenori Ochiai, Hideki Tanzawa

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Ku80 is an important component of DNA double-strand break repair, and Ku80 deficiency leads to extreme sensitivity to ionizing radiation. We studied whether radiation therapy combined with Ku80 silencing by small interfering RNA enhances radiation sensitivity in vitro and in vivo. Seven human cancer cell lines were transfected with Ku80 siRNA included in hemagglutinating virus of Japan envelope vector. H1299 cells were implanted into male BALB/C nu/nu nude mice treated with Ku80 siRNA and irradiation. The survival rate of cell lines transfected with Ku80 siRNA decreased by 10% to 26% with 2-Gy irradiation compared with untransfected cell lines. The gamma-H2AX phosphorylation-positive rates of Ku80 siRNA combined treatment 0.5 h after irradiation in A549 cells and 6 h in H1299 cells were significantly higher (77.6%, p=0.033 and 76.7%, p=0.026, respectively), compared with the groups not treated with siRNA. H1299 xenograft tumors treated with combined therapy decreased in volume and re-grew slowly compared with radiation alone. Our results indicate that combined therapy consisting of Ku80 siRNA and irradiation contributes to inhibition of tumor growth and may be a novel strategy for cancer treatment.

Original languageEnglish
Pages (from-to)1477-1484
Number of pages8
JournalInternational Journal of Oncology
Volume30
Issue number6
Publication statusPublished - 2007 Jun
Externally publishedYes

    Fingerprint

Keywords

  • HVJ envelope
  • Ku80
  • Radiation sensitivity
  • Small interfering RNA

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Nimura, Y., Kawata, T., Uzawa, K., Okamura, J., Liu, C., Saito, M., Shimada, H., Seki, N., Nakagawara, A., Ito, H., Ochiai, T., & Tanzawa, H. (2007). Silencing Ku80 using small interfering RNA enhanced radiation sensitivity in vitro and in vivo. International Journal of Oncology, 30(6), 1477-1484.