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双歧杆菌介导的可溶性 fms 样酪氨酸激酶 1 基因治疗系统对小鼠 Lewis 肺癌的抗肿瘤作用。

Antitumor effect of sFlt-1 gene therapy system mediated by Bifidobacterium Infantis on Lewis lung cancer in mice.

机构信息

Department of Abdominal Cancer, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China.

出版信息

Cancer Gene Ther. 2011 Dec;18(12):884-96. doi: 10.1038/cgt.2011.57. Epub 2011 Sep 16.

Abstract

Soluble fms-like tyrosine kinase receptor (sFlt-1) is a soluble form of extramembrane part of vascular endothelial growth factor receptor-1 (VEGFR-1) that has antitumor effects. Bifidobacterium Infantis is a kind of non-pathogenic and anaerobic bacteria that may have specific targeting property of hypoxic environment inside of solid tumors. The aim of this study was to construct Bifidobacterium Infantis-mediated sFlt-1 gene transferring system and investigate its antitumor effect on Lewis lung cancer (LLC) in mice. Our results demonstrated that the Bifidobacterium Infantis-mediated sFlt-1 gene transferring system was constructed successfully and the system could express sFlt-1 at the levels of gene and protein. This system could not only significantly inhibit growth of human umbilical vein endothelial cells induced by VEGF in vitro, but also inhibit the tumor growth and prolong survival time of LLC C57BL/6 mice safely. These data suggest that Bifidobacterium Infantis-mediated sFlt-1 gene transferring system presents a promising therapeutic approach for the treatment of cancer.

摘要

可溶性 fms 样酪氨酸激酶受体(sFlt-1)是血管内皮生长因子受体-1(VEGFR-1)的跨膜外部分的可溶性形式,具有抗肿瘤作用。婴儿双歧杆菌是一种无致病性的厌氧菌,可能对实体瘤内部的缺氧环境具有特定的靶向性。本研究旨在构建婴儿双歧杆菌介导的 sFlt-1 基因转移系统,并研究其对小鼠 Lewis 肺癌(LLC)的抗肿瘤作用。我们的结果表明,成功构建了婴儿双歧杆菌介导的 sFlt-1 基因转移系统,该系统可以在基因和蛋白水平上表达 sFlt-1。该系统不仅可以显著抑制 VEGF 诱导的人脐静脉内皮细胞的生长,而且可以安全抑制 LLC C57BL/6 小鼠的肿瘤生长并延长其生存时间。这些数据表明,婴儿双歧杆菌介导的 sFlt-1 基因转移系统为癌症的治疗提供了一种很有前途的治疗方法。

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