The combination of Hsp90 inhibitor 17AAG and heavy-ion irradiation provides effective tumor control in human lung cancer cells.
The combination of Hsp90 inhibitor 17AAG and heavy-ion irradiation provides effective tumor control in human lung cancer cells.
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DOI：
10.1002/cam4.377
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发表时间：
2015-03
期刊：
影响因子：
4
通讯作者：
Okayasu, Ryuichi
中科院分区：
文献类型：
--
作者：
Hirakawa, Hirokazu;Fujisawa, Hiroshi;Masaoka, Aya;Noguchi, Miho;Hirayama, Ryoichi;Takahashi, Momoko;Fujimori, Akira;Okayasu, Ryuichi
热休克蛋白90抑制剂由于其对肿瘤细胞的选择性而成为研究较多的抗肿瘤药物。Hsp 90抑制剂和常规光子辐射的联合治疗也显示出比单独辐射更有效的肿瘤生长延迟。然而，关于Hsp 90抑制剂和重离子照射的联合治疗知之甚少。在这项研究中，SQ5人肺肿瘤细胞在体外用于克隆形成细胞存活，并在体内使用17-烯丙基氨基-17-去甲氧基格尔德霉素（17 AAG）预处理和碳离子照射后的小鼠异种移植模型用于肿瘤生长延迟测量。还沿着DNA双链断裂（DSB）修复相关蛋白的表达评估了DNA双链断裂（DSB）的修复。还进行了联合处理后的细胞周期分析。17 AAG和碳离子的组合治疗在体外和体内研究中均显示出有希望的治疗选择。这种有效性的一个可能原因是17 AAG对同源重组修复的抑制。与单独碳离子处理相比，更强化的G2期细胞周期延迟也与联合处理相关。我们的研究结果表明，Hsp 90抑制和重离子照射的组合提供了一个新的有效的治疗实体瘤的治疗选择。
Hsp90 inhibitors have become well-studied antitumor agents for their selective property against tumors versus normal cells. The combined treatment of Hsp90 inhibitor and conventional photon radiation also showed more effective tumor growth delay than radiation alone. However, little is known regarding the combined treatment of Hsp90 inhibitor and heavy-ion irradiation. In this study, SQ5 human lung tumor cells were used in vitro for clonogenic cell survival and in vivo for tumor growth delay measurement using a mouse xenograft model after 17-allylamino-17-demethoxygeldanamycin (17AAG) pretreatment and carbon ion irradiation. Repair of DNA double strand breaks (DSBs) was also assessed along with expressions of DSB repair-related proteins. Cell cycle analysis after the combined treatment was also performed. The combined treatment of 17AAG and carbon ions revealed a promising treatment option in both in vitro and in vivo studies. One likely cause of this effectiveness was shown to be the inhibition of homologous recombination repair by 17AAG. The more intensified G2 cell cycle delay was also associated with the combined treatment when compared with carbon ion treatment alone. Our findings indicate that the combination of Hsp90 inhibition and heavy-ion irradiation provides a new effective therapeutic alternative for treatment of solid tumors.
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影响因子：
5.7
作者：
Koll TT;Feis SS;Wright MH;Teniola MM;Richardson MM;Robles AI;Bradsher J;Capala J;Varticovski L
通讯作者：
Varticovski L
影响因子：
5
作者：
Niewidok, Natalia;Wack, Linda-Jacqueline;Djuzenova, Cholpon S.
通讯作者：
Djuzenova, Cholpon S.
DOI：
10.1158/1078-0432.ccr-11-1000
发表时间：
2012-01-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Neckers L;Workman P
通讯作者：
Workman P
影响因子：
11.2
作者：
Cui, Xing;Oonishi, Kazuhiko;Okayasu, Ryuichi
通讯作者：
Okayasu, Ryuichi
DOI：
10.1073/pnas.1203326109
发表时间：
2012-08-21
影响因子：
11.1
作者：
Stecklein, Shane R.;Kumaraswamy, Easwari;Jensen, Roy A.
通讯作者：
Jensen, Roy A.