Synergistic Effect of Sorafenib and Radiation on Human Oral Carcinoma in vivo.
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.
Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, No. 155, Sec. 2, Li-Nong St., Bei-tou, Taipei 112, Taiwan.
Fei-Ting
FT
Hsu
Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, No. 155, Sec. 2, Li-Nong St., Bei-tou, Taipei 112, Taiwan.
Betty
B
Chang
Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, No. 155, Sec. 2, Li-Nong St., Bei-tou, Taipei 112, Taiwan.|Department of Radiation Oncology, Mackay Memorial Hospital, No. 45, Minsheng Rd., Tamsui District, New Taipei City 251, Taiwan.
John Chun-Hao
JC
Chen
Department of Radiation Oncology, National Yang-Ming University Hospital, I-Lan 260, Taiwan.
I-Tsang
IT
Chiang
Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, No. 155, Sec. 2, Li-Nong St., Bei-tou, Taipei 112, Taiwan.|Department of Radiation Oncology, National Yang-Ming University Hospital, I-Lan 260, Taiwan.
Yu-Chang
YC
Liu
Department of Anatomical Pathology, Cheng-Hsin General Hospital, Taipei 112, Taiwan.
Wei-Kang
WK
Kwang
Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, No. 155, Sec. 2, Li-Nong St., Bei-tou, Taipei 112, Taiwan.|Biophotonics and Molecular Imaging Research Center, National Yang-Ming University, Taipei, Taiwan.
Jeng-Jong
JJ
Hwang
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology / Q000532:radiotherapy*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology / Q000532:radiotherapy*; D049109:Cell Proliferation / Q000187:drug effects / Q000528:radiation effects; D003131:Combined Modality Therapy; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000528:radiation effects; D006801:Humans; D051379:Mice; D009062:Mouth Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology / Q000532:radiotherapy*; D016328:NF-kappa B / Q000096:biosynthesis; D009536:Niacinamide / Q000008:administration & dosage / Q000031:analogs & derivatives; D010671:Phenylurea Compounds / Q000008:administration & dosage; D000077157:Sorafenib; D023041:Xenograft Model Antitumor Assays
D016328:NF-kappa B; D010671:Phenylurea Compounds; D009536:Niacinamide; D000077157:Sorafenib