Background: Antiangiogenic therapies are considered promising for the treatment of glioblastoma (GB). The noncollagenous\nC-terminal globular NC1 domain of type VIII collagen a1 chain, Vastatin, is an endogenous antiangiogenic\npolypeptide. Sustained enhanced expression of Vastatin was shown to inhibit tumour growth and metastasis in murine\nhepatocellular carcinoma models. In this study, we further explored the efficacy of Vastatin in the treatment of GB\nxenografts.\nMethod: Treatment of Vastatin was carried out using a nanopolymer gene vector PEI600-CyD-Folate (H1). Antiangiogenic\neffect of Vastatin was tested in vitro by using co-culture system and conditioned medium. An orthotopic GB murine\nmodel was established to examine the in vivo therapeutic effect of Vastatin alone treatment and its combination with\ntemozolomide.\nResults: Vastatin gene transfection mediated by H1 could target tumour cells specifically and suppress the\nproliferation of microvessel endothelial cells (MECs) through a paracrine inhibition manner. Enhancing Vastatin\nexpression by intracerebral injection of H1-Vastatin significantly prolonged animal survival from 48 to 75 days in\nGB murine model, which was comparable to the effect of Endostatin, the most studied endogenous antiangiogenic\npolypeptide. The diminished presence of CD34 positive cells in the GB xenografts suggested that Vastatin induced\nsignificant antiangiogenesis. Moreover, a synergistic effect in extending survival was detected when H1-Vastatin was\nadministered with temozolomide (TMZ) in GB chemoresistant murine models.\nConclusion: Our results suggest, for the first time, that Vastatin is an antiangiogenic polypeptide with significant potential\ntherapeutic benefit for GB. H1-Vastatin gene therapy may have important implications in re-sensitizing recurrent GB to\nstandard chemotherapeutic agents.
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