Hyperthermia enhances 17-DMAG efficacy in hepatocellular carcinoma cells with aggravated DNA damage and impaired G2/M transition.
Hyperthermia enhances 17-DMAG efficacy in hepatocellular carcinoma cells with aggravated DNA damage and impaired G2/M transition.
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热疗增强 17-DMAG 对 DNA 损伤加剧和 G2/M 期转变受损的肝细胞癌细胞的功效
DOI：
10.1038/srep38072
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发表时间：
2016-12-02
影响因子：
4.6
通讯作者：
Chen X
中科院分区：
文献类型：
--
作者：
Huang Z;Zhou X;He Y;Ke X;Wen Y;Zou F;Chen X
由于缺乏有效的治疗方法，肝细胞癌（HCC）是世界范围内生存率低的恶性肿瘤之一。热疗和化疗的组合在几种腹部肿瘤中显示出有希望的结果，但是肿瘤中HSP 90的高表达减弱了热疗的功效。因此，热疗和抑制HSP 90的结合可能是一种可行的治疗肝癌的策略。将一种肝细胞系（L02）和两种HCC细胞系（Huh 7和HepG 2）在42 °C下加热0、0.5或4小时，加入或不加入100 nM 17-二甲基氨基乙基氨基-17-脱甲氧基格尔德霉素（17-DMAG）。联合用药组肝癌细胞G2/M期阻滞率和凋亡率明显高于对照组，这可能与活性氧增多和DNA损伤严重有关。HCC细胞的热休克/17-DMAG共处理也使CDK 1、细胞周期蛋白B1和CDC 25 C不稳定，伴随着M期细胞比例的降低。此外，联合治疗损害了HSP 90 α与CDC 37和CDK 1的相互作用，并伴有可溶性CDK 1的减少。17-DMAG与1.5小时全身热疗治疗的组合在异种移植小鼠模型中减弱了肿瘤生长。这些结果表明，热疗对17-DMAG敏感，热疗与17-DMAG联合治疗肝癌可能是一种潜在的治疗策略。
Due to the lack of effective treatment, hepatocellular carcinoma (HCC) is one of the malignancies with low survival rates worldwide. Combination of hyperthermia and chemotherapy has shown promising results in several abdominal tumours, but high expression of HSP90 in tumours attenuated the efficacy of hyperthermia. Thus a combination of hyperthermia and inhibition of HSP90 might be a feasible therapeutic strategy for HCC. One hepatic cell line (L02) and two HCC cell lines (Huh7 and HepG2) were heated at 42 °C for 0, 0.5 or 4 h with or without 100 nM 17-dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG). HCC cells of the combination group exhibited more G2/M arrest and higher apoptotic rates which might result from suffering from more reactive oxygen species and serious DNA damage. Heat shock/17-DMAG co-treatment of HCC cells also destabilized CDK1, Cyclin B1 and CDC25C with a concomitant decreased proportion of cells in the M phase. Furthermore, co-treatment impaired the interaction of HSP90α with CDC37 and with CDK1, accompanied with decreased soluble CDK1. Combination of 17-DMAG with a 1.5-h whole body hyperthermia treatment attenuated tumour growth in xenograft mice models. These results suggest hyperthermia sensitize HCC to 17-DMAG, and combination of hyperthermia with 17-DMAG might be a potential therapeutic strategy for HCC.
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影响因子：
3.1
作者：
Cihoric, Nikola;Tsikkinis, Alexandros;Ghadjar, Pirus
通讯作者：
Ghadjar, Pirus
DOI：
10.1186/s13014-015-0462-0
发表时间：
2015-08-07
期刊：
Radiation oncology (London, England)
影响因子：
--
作者：
Oei AL;Vriend LE;Crezee J;Franken NA;Krawczyk PM
通讯作者：
Krawczyk PM
DOI：
10.1016/j.jconrel.2013.04.006
发表时间：
2013-08-28
期刊：
Journal of controlled release : official journal of the Controlled Release Society
影响因子：
--
作者：
Larson N;Gormley A;Frazier N;Ghandehari H
通讯作者：
Ghandehari H
影响因子：
3.1
作者：
Kraybill, WG;Olenki, T;Repasky, EA
通讯作者：
Repasky, EA
影响因子：
4
作者：
Chen S;Sang N
通讯作者：
Sang N