Synergistic Effect of Sorafenib and Radiation on Human Oral Carcinoma in vivo.
Synergistic Effect of Sorafenib and Radiation on Human Oral Carcinoma in vivo.
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DOI：
10.1038/srep15391
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发表时间：
2015-10-21
影响因子：
4.6
通讯作者：
Hwang JJ
中科院分区：
文献类型：
--
作者：
Hsu FT;Chang B;Chen JC;Chiang IT;Liu YC;Kwang WK;Hwang JJ
口腔鳞状细胞癌常引起骨侵犯，导致预后不良，影响患者的生活质量。在此，我们将放射与索拉非尼相结合，以评估原位人类 OSCC 小鼠模型中对肿瘤进展和骨侵蚀的联合作用。治疗过程分为以下几组：（a）正常（无肿瘤）； (b) 对照（有肿瘤）； (c) 索拉非尼（10mg/kg/天）； (d) 辐射（单剂量6 Gy）； (e) 预处理（放射前索拉非尼治疗 3 天），以及 (f) 同步治疗（索拉非尼和放射在同一天进行）。预处理组对肿瘤生长的抑制作用以及肿瘤组织中NF-κB p65表达水平最显着。 EMSA和Western blot显示DNA/NF-κB活性和NF-κB相关蛋白的表达下调。值得注意的是，显微 CT 成像发现，接受索拉非尼和辐射联合治疗的小鼠下颌骨和颧骨几乎没有损伤。总之，索拉非尼联合放疗可抑制辐射诱导的 NF-κB 活性及其下游蛋白，从而导致放射抗性和肿瘤发生。此外，骨质破坏也减少，表明联合治疗可能是对抗人类 OSCC 的潜在策略。
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.