Endostatin improves radioresponse and blocks tumor revascularization after radiation therapy for A431 xenografts in mice
Endostatin improves radioresponse and blocks tumor revascularization after radiation therapy for A431 xenografts in mice
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DOI：
10.1016/j.ijrobp.2006.10.030
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发表时间：
2007-03-01
影响因子：
7
通讯作者：
O'Reilly, Michael S.
中科院分区：
文献类型：
--
作者：
Itasaka, Satoshi;Komaki, Ritsuko;O'Reilly, Michael S.
目的：单独使用抗血管生成药物治疗晚期恶性肿瘤的临床试验令人失望，但临床前研究表明，联合放射治疗可以提高抗肿瘤疗效。为了检验抗血管生成治疗联合放射治疗可以克服抗血管生成单一治疗的局限性这一假设，我们研究了内皮抑素联合放射治疗对小鼠腿部肌肉内生长的 A431 人表皮样癌生长和血管化的影响。 方法和材料：对已形成 A431 人表皮样腿部肿瘤的小鼠进行放射、内皮抑素、放射和内皮抑素两者或载体对照治疗。重复实验，各组小鼠在照射后2、7、10天处死，获取肿瘤组织，进一步分析抗肿瘤、抗血管和抗血管生成反应的动力学。结果：内皮抑素增强了放射的抗肿瘤作用，联合治疗组观察到延长的无病生存期。辐射后肿瘤内皮细胞增殖增加，但同时给予内皮抑素则被阻断，并且内皮抑素与辐射的组合在辐射后48小时内增强内皮细胞凋亡。放射治疗后肿瘤中血管内皮生长因子、白细胞介素-8和基质金属蛋白酶-2的表达增加，并且这种增加被同时给予内皮抑素所阻断。结论：这些数据表明内皮抑素可以阻断放射治疗后肿瘤的血运重建，从而增强放射反应。 (c) 2007 爱思唯尔公司
Purpose: Clinical trials of antiangiogenic agents used alone for advanced malignancy have been disappointing but preclinical studies suggest that the addition of radiation therapy could improve antitumor efficacy. To test the hypothesis that antiangiogenic therapy combined with radiation therapy can overcome the limitations of antiangiogenic monotherapy, we studied the effects of endostatin combined with radiation on the growth and vascularization of A431 human epidermoid carcinomas growing intramuscularly in the legs of mice.Methods and Materials: Mice with established A431 human epidermoid leg tumors were treated with radiation, endostatin, both -radiation and endostatin, or vehicle control. The experiment was repeated and mice from each group were killed at 2, 7, and 10 days after irradiation so that tumor tissue could be obtained to further analyze the kinetics of the antitumor, antivascular, and antiangiogenic response to therapy.Results: Endostatin enhanced the antitumor effects of radiation, and prolonged disease-free survival was observed in the combined treatment group. Endothelial cell proliferation was increased in tumors after irradiation but was blocked by the concurrent administration of endostatin, and the combination of endostatin with radiation enhanced endothelial cell apoptosis within 48 h after irradiation. Expression of vascular endothelial growth factor, interleukin-8, and matrix metalloproteinase-2 were increased in tumors after irradiation, and this increase was blocked by concurrent administration of endostatin.Conclusion: These data indicate that endostatin can block tumor revascularization after radiation therapy and thereby augment radioresponse. (c) 2007 Elsevier Inc.