Intratumoral gene therapy of malignant brain tumor in a rat model with angiostatin delivered by adeno-associated viral (AAV) vector
Intratumoral gene therapy of malignant brain tumor in a rat model with angiostatin delivered by adeno-associated viral (AAV) vector
复制标题
DOI：
10.1038/sj.gt.3301616
复制
发表时间：
2002-01-01
期刊：
影响因子：
5.1
通讯作者：
Xiao, X
中科院分区：
文献类型：
--
作者：
Ma, HI;Lin, SZ;Xiao, X
我们利用携带血管抑素基因的重组腺相关病毒(AAV)作为抗血管生成的策略来治疗C6胶质瘤/Wistar大鼠模型中的恶性脑瘤。血管抑素作为一种有效的血管生成抑制剂，通过抑制肿瘤新生血管的形成，显示出作为一种抗癌药物的良好前景。然而，需要体内持续的蛋白质输送才能达到治疗效果。AAV载体已被证明能够在体内持续和高水平地表达基因，因此非常适合于这一目的。在这项研究中，我们在基因治疗前7天将5×101 C6胶质瘤细胞植入大鼠脑内。瘤内注射高滴度的AAV-Angiostatin载体可有效地抑制肿瘤，并使40%的治疗大鼠长期存活，而对照组AAV-GFP载体没有任何治疗益处。此外，我们还研究了携带自杀性胸苷激酶基因的腺病毒载体和AAV-Angiostatin载体的联合基因治疗，联合治疗提供了最佳的抑瘤效果，并将治疗大鼠的长期存活率提高到55%。我们的研究表明，AAV作为一种安全有效的载体用于脑肿瘤的抗血管生成基因治疗是有潜力的。
We have utilized a recombinant adeno-associated viral (AA V) vector carrying the angiostatin gene as an anti-angiogenesis strategy to treat the malignant brain tumor in a C6 glioma/Wistar rat model. Angiostatin, as a potent angiogenesis-inhibitor, shows high promises as an anti-cancer drug through the inhibition of tumor neovessel formation. However, sustained in vivo protein delivery is required to achieve the therapeutic effects. The AA V vector has been proven to be able to deliver sustained and high-level gene expression in vivo, and therefore, is well suited to such a purpose. In this study, we implanted 5 x 101 C6 glioma cells into the rat brain 7 days before gene therapy. Intratumoral injection of a high-titer AAV-angiostatin vector has rendered efficacious tumor suppression and resulted in long-term survival in 40% of the treated rats, whereas the control AAV-GFP vector did not have any therapeutic benefits. In addition, we have investigated the combined gene therapy of an adenoviral vector carrying the suicidal thymidine kinase gene along with the AAV-angiostatin vector, The combined therapy offered the best tumor-suppressive effects and increased long-term survival to 55% in the treated rats. Our study has demonstrated the potential of using AAV as a safe and effective vector for anti-angiogenic gene therapy of brain tumors.