title: Inhibition of tribbles protein-1 attenuates radioresistance in human glioma cells.
abstract: Radiotherapy is one of the remedies in the treatment of glioma. The radioresistance is a major drawback, of which the mechanism is unclear. Tribble protein and histone deacetylase are involved in the cancer pathogenesis. This study aims to test a hypothesis that the histone deacetylase inhibitors attenuate the radioresistance in human glioma cells. In this study, human glioma cells were cultured. The cells were treated with irradiation with or without a histone deacetylase inhibitor, butyrate. Apoptosis of the glioma cells was assessed by flow cytometry. The results showed that human glioma cells expressed a low level of Trib1, which was significantly up regulated by exposure to small doses (2 Gy/day for 4 days) of irradiation. Trib1-deficient glioma cells showed an enhanced response to irradiation-induced apoptosis. Exposure to small doses of irradiation, Trib1 formed a complex with pHDAC1 (phosphor histone deacetylase-1) to inhibit p53 expression in glioma cells. The presence of HDAC1 inhibitor, butyrate or parthenolide, significantly enforced irradiation-induced glioma cell apoptosis. In conclusion, the Trib1 plays a critical role in the development of radioresistance of glioma cells. The data suggest that inhibition of Trib1 or HDAC1 has the potential to prevent or attenuate the radioresistance.
authors.affiliation: Department of Hepatobiliary Surgery, Guilin Medical University, Affiliated Hospital, and Laboratory of Liver Injury and Repair Molecular Medicine, Guilin Medical University, Guilin, 541001, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Tang
authors.affiliation: Department of Neurosurgery, The First Hospital of Jilin University, Changchun, 130021, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wu
authors.affiliation: Affiliated Zhongshan Hospital of Dalian University, Dalian, 116001, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Affiliated Zhongshan Hospital of Dalian University, Dalian, 116001, China.
authors.forename: Yongjin
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Affiliated Zhongshan Hospital of Dalian University, Dalian, 116001, China.
authors.forename: Yifen
authors.initials: Y
authors.lastname: Cui
authors.affiliation: Affiliated Zhongshan Hospital of Dalian University, Dalian, 116001, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Wu
authors.affiliation: Affiliated Zhongshan Hospital of Dalian University, Dalian, 116001, China.
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Wei
authors.affiliation: Department of Hepatobiliary Surgery, Guilin Medical University, Affiliated Hospital, and Laboratory of Liver Injury and Repair Molecular Medicine, Guilin Medical University, Guilin, 541001, China.
authors.forename: Guangying
authors.initials: G
authors.lastname: Qi
authors.affiliation: Department of Hepatobiliary Surgery, Guilin Medical University, Affiliated Hospital, and Laboratory of Liver Injury and Repair Molecular Medicine, Guilin Medical University, Guilin, 541001, China.
authors.forename: Xingsi
authors.initials: X
authors.lastname: Liang
authors.affiliation: Department of Hepatobiliary Surgery, Guilin Medical University, Affiliated Hospital, and Laboratory of Liver Injury and Repair Molecular Medicine, Guilin Medical University, Guilin, 541001, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Tang
authors.affiliation: Department of Neurosurgery, The First Hospital of Jilin University, Changchun, 130021, China.
authors.forename: Yunqian
authors.initials: Y
authors.lastname: Li
authors.affiliation: Affiliated Zhongshan Hospital of Dalian University, Dalian, 116001, China.
authors.forename: Wenhai
authors.initials: W
authors.lastname: Fan
mesh_terms: D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D001932:Brain Neoplasms / Q000235:genetics*; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000235:genetics; D005910:Glioma / Q000235:genetics*; D056284:Histone Deacetylase 1 / Q000235:genetics; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000037:antagonists & inhibitors*; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors*; D011836:Radiation Tolerance / Q000187:drug effects* / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000235:genetics; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics
chemical_list: D056572:Histone Deacetylase Inhibitors; D047908:Intracellular Signaling Peptides and Proteins; C493170:TRIB1 protein, human; D016159:Tumor Suppressor Protein p53; D017346:Protein Serine-Threonine Kinases; C110550:HDAC1 protein, human; D056284:Histone Deacetylase 1