Matrix protein of vesicular stomatitis virus: a potent inhibitor of vascular endothelial growth factor and malignant ascites formation
Matrix protein of vesicular stomatitis virus: a potent inhibitor of vascular endothelial growth factor and malignant ascites formation
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水泡性口炎病毒基质蛋白：血管内皮生长因子和恶性腹水形成的有效抑制剂
DOI：
10.1038/cgt.2013.7
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发表时间：
2013-03-01
影响因子：
6.4
通讯作者：
Li, Q.
中科院分区：
文献类型：
--
作者：
Zhou, Y.;Wen, F.;Li, Q.
恶性腹水在各种类型的癌症中很常见，并且难以管理。血管内皮生长因子（VEGF）在恶性腹水中起关键作用。水泡性口炎病毒的基质蛋白（VSVMP）能抑制宿主基因表达，诱导癌细胞凋亡。本研究旨在确定VSVMP是否抑制腹水产生的腹膜癌病腹水的形成。携带H22或MethA细胞的腹膜肿瘤的6-8周龄BALB/c雌性小鼠分别接受50 μ g VSVMP/250 μ g脂质体复合物、50 μ g空质粒/250 μ g脂质体复合物或0.9%NaCl溶液的腹膜内给药，每2天一次，持续3周。给予VSVMP导致显著抑制腹水形成，改善健康状况并延长治疗小鼠的存活时间。腹膜渗透压的降低和肿瘤血管的减少与腹水和血浆中VEGF水平的显著降低相一致。从腹腔冲洗液中收集的漂浮肿瘤细胞的检查显示，在VSMP处理的小鼠中，凋亡细胞的数量明显增加，VEGF mRNA的表达显著下调。我们的数据首次表明，在荷H22或MethA细胞腹膜肿瘤的BALB/c小鼠中，VSVMP可以抑制VEGF的产生并抑制血管生成，从而消除腹水形成。Cancer Gene Therapy（2013）20，178-185; doi：10.1038/cgt.2013.7; 2013年3月1日在线发表
Malignant ascites is common in various types of cancers and is difficult to manage. Vascular endothelial growth factor (VEGF) has a pivotal role in malignant ascites. The matrix protein of vesicular stomatitis virus (VSVMP) has been shown to inhibit host gene expression and induce the apoptosis of cancer cells. The present study was designed to determine whether VSVMP suppresses the formation of ascites in ascites-producing peritoneal carcinomatosis. BALB/c female mice, 6-8 weeks old, bearing peritoneal tumors of H22 or MethA cells received an intraperitoneal administration of 50 mu g VSVMP/250 mu g liposome complexes, 50 mu g empty plasmid/250 mu g liposome complexes or 0.9% NaCl solution, respectively, every 2 days for 3 weeks. Administration of VSVMP resulted in a significant inhibition in ascites formation, improvement in health condition and prolonged survival of the treated mice. Decreased peritoneum osmolarity and reduced tumor vascularity coincided with dramatic reductions in the VEGF level in ascites fluid and plasma. Examination of floating tumor cells collected from the peritoneal wash revealed an apparently increased number of apoptotic cells and profound downregulation of VEGF mRNA in the VSVMP-treated mice. Our data indicate for the first time that in BALB/c mice bearing H22 or MethA cell peritoneal tumors, VSVMP may inhibit VEGF production and suppress angiogenesis, consequently abolishing ascites formation. Cancer Gene Therapy (2013) 20, 178-185; doi:10.1038/cgt.2013.7; published online 1 March 2013