title: Histone deacetylase inhibitor, valproic acid, radiosensitizes the C6 glioma cell linein vitro.
abstract: Valproic acid (VPA) is a well-tolerated drug that is used to treat seizure disorders and that has recently been shown to inhibit histone deacetylase. The present study investigated the effects of VPA on the radiosensitization of the rat C6 glioma cell linein vitro. To select an appropriate treatment concentration and time, MTT and flow cytometry assays were performed to measure the inhibitory effects of VPA at various concentrations and incubation time-points. The radiosensitizing effect of VPA was determined using clonogenic experiments. VPA- and radiation-induced C6 apoptosis was analyzed using quantitative polymerase chain reaction and western blot analysis. Cell proliferation was significantly inhibited by VPA in a time- and dose-dependent manner (P<0.05). VPA enhanced radiation-induced C6 cell death and there was clear inhibition of clonogenic formation [sensitizer enhancement ratio (SER), 1.30]. This effect was closely associated with the concentration of VPA. VPA treatment decreased the mRNA and protein levels of Bcl-2, whereas increased changes were detected with Bax. At a concentration of 0.5 mmol/l, VPA had a low toxicity and enhanced the radiosensitization of the C6 cells. VPA may radiosensitize glioma cells by inhibiting cellular proliferation and inducing apoptosis by regulating apoptosis-related molecular changes.
authors.affiliation: Cancer Centre, The Second Hospital of Shandong University, Jinan, Shandong 250033, P.R. China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Cancer Centre, The Second Hospital of Shandong University, Jinan, Shandong 250033, P.R. China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of Radiotherapy, Shandong Jining First People's Hospital, Jining, Shandong 272011, P.R. China.
authors.forename: Han
authors.initials: H
authors.lastname: Wang
authors.affiliation: Cancer Centre, The Second Hospital of Shandong University, Jinan, Shandong 250033, P.R. China.
authors.forename: Junjie
authors.initials: J
authors.lastname: Niu
authors.affiliation: Cancer Centre, The Second Hospital of Shandong University, Jinan, Shandong 250033, P.R. China.
authors.forename: Huaying
authors.initials: H
authors.lastname: Hou
authors.affiliation: Cancer Centre, The Second Hospital of Shandong University, Jinan, Shandong 250033, P.R. China.
authors.forename: Yuhua
authors.initials: Y
authors.lastname: Jiang
keywords: C6; X-ray; apoptosis; gliomas; histone deacetylase inhibitors; in vitro; radiosensitization; valproic acid