転写因子NF-κB活性の抑制による口腔扁平上皮癌の放射線感受性の増強(若野洋一歯科臨床医学奨励賞受賞講演)

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The nuclear factor κB (NF-κB) plays an important role in the development and progression of cancers. We had already reported that NF-κB activity in head and neck carcinoma cells was significantly higher than that in normal oral epithelial cells due to the enhanced phosphorylation and degradation of IκBα protein. We examined the mechanisms underlying the enhancement of radiosensitivity to γ-irradiation (IR) in human oral carcinoma cells (B88) in which NF-κB activity was constitutively suppressed. Super-repressor form of IκBα cDNA-transfected cell clone (B88mI) and empty vector-transfected cell clone (B88neo) was established. We found that the tumor forming ability in nude mice of B88mI clones was significantly lower than that of B88 or B88neo. This suppressed ability in tumorigenicity was attributed to the down regulation of the expression of interleukin (IL)-1 α, IL-6, IL-8 and vascular endothelial growth factor (VEGF) in B88mI cell clones as compared to that in B88 or B88neo. IR induced a much greater degree of apoptosis, as evidenced by flow cytometry analysis and annexin V staining, in B88mI cell clone than B88 or B88neo. When tumor-bearing nude mice were treated with IR, the suppression of tumor growth was significantly augmented in B88mI cell clones as compared to that in B88 or B88neo. These findings indicate that inhibition of NF-κB activity by introducing a super-repressor form of IκBα cDNA into oral cancer cells led to a drastic decrease in tumorigenicity in nude mice and an acquisition of enhanced radiosensitization. Therefore, targeting NF-κB may be a potential approach to controlling the growth of human cancers.

著者

茂木勝美
徳島大学大学院ヘルスバイオサイエンス研究部口腔腫瘍制御学分野

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