Synergistic Effect of Sorafenib and Radiation on Human Oral Carcinoma in vivo.

Abstract

Oral squamous cell carcinoma often causes bone invasion resulting in poor prognosis and affects the quality of life for patients. Herein, we combined radiation with sorafenib, to evaluate the combination effect on tumor progression and bone erosion in an in situ human OSCC-bearing mouse model. Treatment procedure were arranged as following groups: (a) normal (no tumor); (b) control (with tumor); (c) sorafenib (10 mg/kg/day); (d) radiation (single dose of 6 Gy); (e) pretreatment (sorafenib treatment for 3 days prior to radiation), and (f) concurrent treatment (sorafenib and radiation on the same day). The inhibition of tumor growth and expression level of p65 of NF-κB in tumor tissues were the most significant in the pretreatment group. EMSA and Western blot showed that DNA/NF-κB activity and the expressions of NF-κB-associated proteins were down-regulated. Notably, little to no damage in mandibles and zygomas of mice treated with combination of sorafenib and radiation was found by micro-CT imaging. In conclusion, sorafenib combined with radiation suppresses radiation-induced NF-κB activity and its downstream proteins, which contribute to radioresistance and tumorigenesis. Additionally, bone destruction is also diminished, suggesting that combination treatment could be a potential strategy against human OSCC.

• Authors: Fei-Ting Hsu, Betty Chang, John Chun-Hao Chen, I-Tsang Chiang, Yu-Chang Liu, Wei-Kang Kwang, Jeng-Jong Hwang
• Journal: Scientific reports (Sci Rep) Vol. 5 Pg. 15391 (Oct 21 2015) ISSN: 2045-2322 [Electronic] England
• PMID: 26487364 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• NF-kappa B
• Phenylurea Compounds
• Niacinamide
• Sorafenib

Topics

• Animals
• Apoptosis (drug effects, radiation effects)
• Bone Neoplasms (drug therapy, genetics, pathology, radiotherapy)
• Carcinoma, Squamous Cell (drug therapy, genetics, pathology, radiotherapy)
• Cell Proliferation (drug effects, radiation effects)
• Combined Modality Therapy
• Gene Expression Regulation, Neoplastic (drug effects, radiation effects)
• Humans
• Mice
• Mouth Neoplasms (drug therapy, genetics, pathology, radiotherapy)
• NF-kappa B (biosynthesis)
• Niacinamide (administration & dosage, analogs & derivatives)
• Phenylurea Compounds (administration & dosage)
• Sorafenib
• Xenograft Model Antitumor Assays