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

• Published in: Scientific reports 2015-10, Vol.5 (1), p.15391-15391, Article 15391
• Main Authors: Hsu, Fei-Ting, Chang, Betty, Chen, John Chun-Hao, Chiang, I-Tsang, Liu, Yu-Chang, Kwang, Wei-Kang, Hwang, Jeng-Jong
• Format: Article
• Language: English
• Subjects: 13/109; 14/63; 45/41; 59/5; 631/67/1059/602; 631/67/1665; 631/67/2321; 64/60; 82/51; 82/80; 96/2; 96/95; Animals; Apoptosis - drug effects; Apoptosis - radiation effects; Bone Neoplasms - drug therapy; Bone Neoplasms - genetics; Bone Neoplasms - pathology; Bone Neoplasms - radiotherapy; Carcinoma, Squamous Cell - drug therapy; Carcinoma, Squamous Cell - genetics; Carcinoma, Squamous Cell - pathology; Carcinoma, Squamous Cell - radiotherapy; Cell Proliferation - drug effects; Cell Proliferation - radiation effects; Combined Modality Therapy; Computed tomography; Deoxyribonucleic acid; DNA; Gene Expression Regulation, Neoplastic - drug effects; Gene Expression Regulation, Neoplastic - radiation effects; Humanities and Social Sciences; Humans; Mandible; Mice; Mouth Neoplasms - drug therapy; Mouth Neoplasms - genetics; Mouth Neoplasms - pathology; Mouth Neoplasms - radiotherapy; multidisciplinary; NF-kappa B - biosynthesis; Niacinamide - administration & dosage; Niacinamide - analogs & derivatives; Oral carcinoma; Oral squamous cell carcinoma; Phenylurea Compounds - administration & dosage; Quality of life; Radioresistance; Rodents; Science; Squamous cell carcinoma; Tumorigenesis; Xenograft Model Antitumor Assays
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep15391

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.