Hyperthermia enhances 17-DMAG efficacy in hepatocellular carcinoma cells with aggravated DNA damage and impaired G2/M transition

摘要: Due to the lack of effective treatment, hepatocellular carcinoma (HCC) is one malignancies with low survival rates worldwide. Combination hyperthermia and chemotherapy has shown promising results in several abdominal tumours, but high expression HSP90 tumours attenuated efficacy hyperthermia. Thus a combination inhibition might be feasible therapeutic strategy for HCC. One hepatic cell line (L02) two HCC lines (Huh7 HepG2) were heated at 42 °C 0, 0.5 or 4 h without 100 nM 17-dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG). cells group exhibited more G2/M arrest higher apoptotic which result from suffering reactive oxygen species serious DNA damage. Heat shock/17-DMAG co-treatment also destabilized CDK1, Cyclin B1 CDC25C concomitant decreased proportion M phase. Furthermore, impaired interaction HSP90α CDC37 accompanied soluble CDK1. 17-DMAG 1.5-h whole body treatment tumour growth xenograft mice models. These suggest sensitize 17-DMAG, potential