Sorafenib potentiates irradiation effect in hepatocellular carcinoma in vitro and in vivo

Wen Yu; Ke Gu; Zhan Yu; Dexiao Yuan; Mingyuan He; Ningyi Ma; Songtao Lai; Jiandong Zhao; Zhigang Ren; Xiaomeng Zhang; Chunlin Shao; Guo-Liang Jiang

doi:10.1016/j.canlet.2012.10.024

Sorafenib potentiates irradiation effect in hepatocellular carcinoma in vitro and in vivo

Cancer Lett. 2013 Feb 1;329(1):109-17. doi: 10.1016/j.canlet.2012.10.024. Epub 2012 Nov 8.

Authors

Wen Yu¹, Ke Gu, Zhan Yu, Dexiao Yuan, Mingyuan He, Ningyi Ma, Songtao Lai, Jiandong Zhao, Zhigang Ren, Xiaomeng Zhang, Chunlin Shao, Guo-Liang Jiang

Affiliation

¹ Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China.

PMID: 23142289
DOI: 10.1016/j.canlet.2012.10.024

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Apoptosis / drug effects
Apoptosis / radiation effects
Carcinoma, Hepatocellular / drug therapy
Carcinoma, Hepatocellular / metabolism
Carcinoma, Hepatocellular / pathology
Carcinoma, Hepatocellular / radiotherapy*
Cell Line, Tumor
Combined Modality Therapy
DNA Damage / drug effects
DNA Repair / drug effects
DNA Repair / radiation effects
Female
Liver Neoplasms / drug therapy
Liver Neoplasms / metabolism
Liver Neoplasms / pathology
Liver Neoplasms / radiotherapy*
MAP Kinase Signaling System / drug effects
Mice
Mice, Inbred BALB C
NF-kappa B / metabolism
Niacinamide / analogs & derivatives*
Niacinamide / pharmacology
Phenylurea Compounds / pharmacology*
Phosphorylation
Radiation-Sensitizing Agents / pharmacology*
Sorafenib
Vascular Endothelial Growth Factor Receptor-2 / metabolism
Xenograft Model Antitumor Assays

Substances

NF-kappa B
Phenylurea Compounds
Radiation-Sensitizing Agents
Niacinamide
Sorafenib
Vascular Endothelial Growth Factor Receptor-2