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Title 

NF-κB inhibition radiosensitizes Ki-Ras-transformed cells to ionizing radiation

Authors 

Bo Yeon KimKyung A KimOSong KwonSun Ok KimMin-Soo KimBeom Seok KimWon Keun OhG D KimM JungJong Seog Ahn

Publisher 

Oxford University Press (OUP)

Issue Date 

2005

Citation 

Carcinogenesis, vol. 26, no. 8, pp. 1395-1403

Keywords 

I kappa B alphaimmunoglobulin enhancer binding proteinK ras proteinmitogen activated protein kinasephosphatidylinositol 3 kinaseproteasome inhibitorprotein bcl 22-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-oneenzyme inhibitorcell death

Abstract 

Most cancer cells show resistance to ionizing radiation (IR)-induced cell death. Recently, Ki-Ras was reported to be responsible for the increased radioresistance. We report here that inhibition of IR-induced activaton of nuclear transcription factor kappa B (NF-κB) but not of either Akt or MAPK kinase (MEK), increased the radiosensitization of Ki-Ras transformed human prostate epithelial 267B1/K-ras cells. Proteosome inhibitor-1 (Pro1) reduced NF-κB activation, and this inhibition was accompanied by increased levels of cytoplasmic IκBα and p65/RelA. However, translocation of p50/ NF-κB1 did not occur on exposure to IR, suggesting the cell-specific involvement of p50 in radiation signaling. Clonogenic cell survival and soft agar assays further confirmed the increased radiosensitivity of 267B1/K-ras cells by proteosome inhibition. In addition, proteosome inhibition enhanced the IR-induced degradation of apoptotic protein caspases 8 and 3, with the level of antiapoptotic protein Bcl-2 being unaffected, suggesting the involvement of an apoptotic process in IR-induced cell death of 267B1/K-ras cells. LY294002 and PD98059, specific inhibitors of phosphatidylinositol-3-kinase (PI3K) and MEK, respectively however, did not affect the radiosensitization. All these results suggest an application of blocking NF-κB activation pathway to the development of anticancer therapeutics in IR-induced radiotherapy of Ki-Ras-transformed cancer cells.

ISSN 

0143-3334

Link 

http://dx.doi.org/10.1093/carcin/bgi081

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2019-05-02


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