ZD6474, a small molecule tyrosine kinase inhibitor, potentiates the anti-tumor and anti-metastasis effects of radiation for human nasopharyngeal carcinoma.
ZD6474, a small molecule tyrosine kinase inhibitor, potentiates the anti-tumor and anti-metastasis effects of radiation for human nasopharyngeal carcinoma.
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DOI：
10.2174/156800910791859506
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发表时间：
2010-08
影响因子：
3
通讯作者：
Shihong Yang;J Wu;Y. Zuo;L. Tan;H. Jia;H. Yan;X. Zhu;M. Zeng;J. Ma;W. Huang
中科院分区：
文献类型：
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作者：
Shihong Yang;J Wu;Y. Zuo;L. Tan;H. Jia;H. Yan;X. Zhu;M. Zeng;J. Ma;W. Huang
目的探讨小分子酪氨酸激酶抑制剂ZD6474增强放疗对人鼻咽癌的抗肿瘤和抗转移作用。实验设计用ZD6474治疗鼻咽癌细胞株和异种移植模型，并与未治疗的对照组小鼠进行比较。结果用ZD6474处理鼻咽癌细胞后，细胞增殖和细胞凋亡率均有不同程度的增加。ZD6474还可显著提高鼻咽癌细胞的放射敏感性，其辐射增敏比(RERS)在1.2~1.6之间。尽管鼻咽癌细胞在放疗后表现出细胞毒性，但鼻咽癌细胞的侵袭和迁移没有受到影响。相反，ZD6474对鼻咽癌细胞的侵袭和迁移有明显的抑制作用。在体外研究辐射和ZD6474的作用时，证实了ZD6474能够抑制辐射诱导的促生存信号通路的激活。在体内，ZD6474显著增强了放射的抗转移作用，而放射治疗和ZD6474的耐受性良好，并对肿瘤生长产生了强烈的抑制作用。结论放疗联合ZD6474治疗鼻咽癌是一种很有前途的治疗策略。
PURPOSE To investigate the capacity for ZD6474, a small molecule tyrosine kinase inhibitor, to enhance anti-tumor and anti-metastasis effects of radiation on human nasopharyngeal carcinoma (NPC). EXPERIMENTAL DESIGN NPC cell lines and xenograft models were evaluated following treatment with ZD6474 and radiation alone and in combination compared with untreated control mice. RESULTS Treatment with ZD6474 enhanced the anti-proliferative effect of radiation on NPC cell lines as detected by cell proliferation and apoptosis assays. ZD6474 also induced a significant increase in the radiosensitivity of NPC cells, with radiation enhancement ratios (RERs) ranging from 1.2 to 1.6. Despite the cytotoxicity exhibited by NPC cells following radiotherapy, the invasion and migration of NPC cells was found to be unaffected. In contrast, treatment with ZD6474 strongly inhibited the invasion and migration of NPC cells. When the administration of radiation and ZD6474 was investigated in vitro, the ability of ZD6474 to inhibit activation of the pro-survival signaling pathways induced by radiation was demonstrated. In vivo, ZD6474 significantly enhanced the anti-metastasis effects of radiation, while treatment with radiation and ZD6474 was found to be well tolerated and resulted in a strong inhibition of tumor growth. CONCLUSIONS Our results suggest the combination of radiation and ZD6474 represents a promising strategy for the treatment of human NPC.