Angiostatin基因真核表达载体的构建及对B16黑色素瘤体内生长抑制作用

CONSTRUCTION OF AN ANGIOSTATIN EUKARYOTIC EXPRESSION VECTOR AND CHARACTERIZATION OF ITS INHIBITORY EFFICIENCY IN B16 MELANOMA BEARING MICE

Angiostatin是一种新发现的对肿瘤生长有特异抑制作用的抗血管生成因子,实验已证实其对多种肿瘤有明显的抑制作用。本文报告构建了含Angiostatin基因的真核表达载体pAG3,通过建立荷瘤小鼠模型来研究Angiostatin对人黑色素瘤B16的原位生长,植入及与化疗药物DTIC的联合作用等来探讨Angiostatin裸DNA肌肉注射的体内抗瘤效应。实验结果表明Angiostatin可明显抑制C57荷瘤小鼠的肿瘤生长;人黑色素瘤B16细胞植入前5天肌肉注射pAG3能显著阻止正常C57小鼠新肿瘤的形成;但在pAG3与DTIC联合化疗实验中,两者未表现出明显的增强效应。本实验为拓展非病毒介导的Angiostatin抗血管生成基因治疗途径奠定了基础。

Recent studies have demonstrated that angiostatin, a newly discovered specific inhibitor of endothelial cells, may significantly suppress the growth of a variety of tumors. We constructed an eukaryotic expression vector containing angiostatin(pAG3 ). To study the effect of pAG3,we intramuscularly injected pAG3 into B16 melanoma bearing C57 mice, we found that pAG3 could obviously inhibit tumor growth and reduce the size of tumors in B16 melanoma bearing C57 mice compared to the untreated control mice. In addition, we also investigated whether pre-treatment of pAG3 can prevent the tumor formation in mice treated with B16 melanoma. Normal C57mice which received 5 days of treatment of pAG3 prior to implanting tumors resulted in the inhibitory effect when compared to control mice. No promotive effect was observed when pAG3 was combined with DTIC (Dacarbazine ). These findings provide a basis for the further development of nonviral delivery of angiogenic gene therapy.