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Synergistic effect of heat shock protein 90 inhibitor, 17-allylamino-17-demethoxygeldanamycin and X-rays, but not carbon-ion beams, on lethality in human oral squamous cell carcinoma cells

Hsp90(熱ショックタンパク質)の阻害剤17-AAG(17-allylamino-17-demethoxygeldanamycin)によるヒト口腔扁平上皮癌細胞株への放射線増感作用はX線では認められたが炭素線照射では認められなかった

武者 篤*; 吉田 由香里*; 高橋 健夫*; 安藤 興一*; 舟山 知夫; 小林 泰彦; 根岸 明秀*; 横尾 聡*; 中野 隆史*

Musha, Atsushi*; Yoshida, Yukari*; Takahashi, Takeo*; Ando, Koichi*; Funayama, Tomoo; Kobayashi, Yasuhiko; Negishi, Akihide*; Yokoo, Satoshi*; Nakano, Takashi*

The purpose of this study is to clarify the effect of a heat shock protein 90 inhibitor, 17-allylamino-17-demethoxygeldanamycin (17-AAG), in combination with X-rays or carbon-ion beams on cell killing in human oral squamous cell carcinoma LMF4 cells. Cell survival was measured by colony formation assay. Cell cycle distribution was analyzed by flow cytometry. Expression of DNA repair-related proteins was investigated by western blotting. The results showed 17-AAG having synergistic effects on cell lethality with X-rays, but not with carbon-ion beams. The 17-AAG decreased G$$_{2}$$/M arrest induced by X-rays, but not by carbon-ion beams. Both X-ray and carbon-ion irradiation up-regulated expression of non-homologous end-joining- associated proteins, Ku70 and Ku80, but 17-AAG inhibited only X-ray-induced up-regulation of Ku70 and Ku80. These results show that 17-AAG with X-rays releases G$$_{2}$$/M phase arrest and then cells carrying misrepaired DNA damage move to G$$_{1}$$ phase. We demonstrate, for the first time, that the radiosensitization effect of 17-AAG is not seen for carbon-ion beams because 17-AAG does not affect these changes.

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パーセンタイル:49.51

分野:Biology

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