title: Sorafenib potentiates irradiation effect in hepatocellular carcinoma in vitro and in vivo.
abstract: The multikinase-inhibition action of sorafenib provides strong rationales for its combination use with radiotherapy. We investigated the in vitro and in vivo effect of sorafenib combined with irradiation on hepatocellular carcinoma (HCC). Sorafenib enhanced radiosensitivity of human HCC cell lines in a schedule-dependent manner. Sorafenib selectively inhibited radiation-induced activation of vascular endothelial growth factor receptor-2 (VEGFR2) and downstream extracellular signal-regulated kinase (ERK) pathway, induced DNA damage and suppressed DNA repair capacity, decreased radiation-activated NF-κB and increased radiation-induced apoptosis. In xenograft experiments, combination treatment produced marked tumor growth delay in both concurrent and sequential schedules. These results suggest that sorafenib could potentiate irradiation effect in HCC, which warrants further investigation for its potential clinical applications.
authors.affiliation: Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Yu
authors.forename: Ke
authors.initials: K
authors.lastname: Gu
authors.forename: Zhan
authors.initials: Z
authors.lastname: Yu
authors.forename: Dexiao
authors.initials: D
authors.lastname: Yuan
authors.forename: Mingyuan
authors.initials: M
authors.lastname: He
authors.forename: Ningyi
authors.initials: N
authors.lastname: Ma
authors.forename: Songtao
authors.initials: S
authors.lastname: Lai
authors.forename: Jiandong
authors.initials: J
authors.lastname: Zhao
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Ren
authors.forename: Xiaomeng
authors.initials: X
authors.lastname: Zhang
authors.forename: Chunlin
authors.initials: C
authors.lastname: Shao
authors.forename: Guo-Liang
authors.initials: GL
authors.lastname: Jiang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy*; D045744:Cell Line, Tumor; D003131:Combined Modality Therapy; D004249:DNA Damage / Q000187:drug effects; D004260:DNA Repair / Q000187:drug effects / Q000528:radiation effects; D005260:Female; D008113:Liver Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000378:metabolism; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000494:pharmacology; D010671:Phenylurea Compounds / Q000494:pharmacology*; D010766:Phosphorylation; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D000077157:Sorafenib; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
chemical_list: D016328:NF-kappa B; D010671:Phenylurea Compounds; D011838:Radiation-Sensitizing Agents; D009536:Niacinamide; D000077157:Sorafenib; D040301:Vascular Endothelial Growth Factor Receptor-2