Guo S W, Che H M, Li W Z
Department of Neurosurgery, First Affiliated Hospital, Medical School of Xi'an Jiaotong University, Shaanxi 710061, P.R. China.
Mol Med Rep. 2010 Nov-Dec;3(6):923-8. doi: 10.3892/mmr.2010.350. Epub 2010 Aug 26.
Angiogenesis is a prerequisite for tumor progression and metastasis. Alphastatin, as an endogenous angiogenesis inhibitor, was recently used as an anticancer agent in several tumor models. We constructed recombinant self-inactivating lentivirus vectors expressing alphastatin and evaluated their ability to transfer genes into human umbilical vein endothelial cells (HUVECs) as well as their antiangiogenic activities in vitro. Recombinant self-inactivating lentiviral vectors efficiently and stably transduced endothelial cells, and lentivirus-transduced HUVECs were capable of sustainedly secreting the antiangiogenesis peptide alphastatin. Long-term expression and secretion of alphastatin resulted in significant inhibition of endothelial cell angiogenesis induced by vascular endothelial growth factor. This report presents the first use of lentivirus-based vectors to deliver the endogenous angiogenesis inhibitor alphastatin, and suggests the potential utility of antiangiogenic gene therapy with lentiviral vectors for the treatment of cancer.
血管生成是肿瘤进展和转移的前提条件。α-抑制素作为一种内源性血管生成抑制剂，最近在几种肿瘤模型中被用作抗癌药物。我们构建了表达α-抑制素的重组自失活慢病毒载体，并评估了它们将基因导入人脐静脉内皮细胞（HUVECs）的能力以及它们在体外的抗血管生成活性。重组自失活慢病毒载体能高效、稳定地转导内皮细胞，慢病毒转导的HUVECs能够持续分泌抗血管生成肽α-抑制素。α-抑制素的长期表达和分泌导致血管内皮生长因子诱导的内皮细胞血管生成受到显著抑制。本报告首次使用基于慢病毒的载体来递送内源性血管生成抑制剂α-抑制素，并提示慢病毒载体抗血管生成基因治疗在癌症治疗中的潜在应用价值。
