针对转移性结直肠癌的 PEDF-DNA 靶向治疗。

Cancer-targeted PEDF-DNA therapy for metastatic colorectal cancer.

机构信息

Department of Critical Care Medicine, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu 610041, China.

出版信息

Int J Pharm. 2020 Feb 25;576:118999. doi: 10.1016/j.ijpharm.2019.118999. Epub 2019 Dec 29.

DOI:10.1016/j.ijpharm.2019.118999

PMID:31893541

Abstract

Colorectal cancer (CRC) is a major cause of cancer-related mortality worldwide. Moreover, metastasis is one of the main causes of death in CRC patients. Nanotechnology-based gene therapy has shown significant therapeutic benefits in recent clinical trials for cancer treatment. Recent studies have shown that pigment epithelium-derived factor (PEDF) protein can inhibit tumor growth and metastasis by anti-angiogenesis and pro-apoptosis. In this study, we prepared a PEDF-DNA-loaded liposome for cancer-targeted gene therapy for metastatic CRC using an iRGD peptide. Our results showed that cancer-targeted PEDF-DNA liposomes (R-LP/PEDF) exhibited enhanced inhibitory effects on invasion, migration, and pro-apoptosis of CRC cells in vitro. In addition, it reduced metastasis tumor nodules in lung and prolonged the survival time in a mouse model of metastatic CRC.

摘要

结直肠癌（CRC）是全球癌症相关死亡的主要原因。此外，转移是 CRC 患者死亡的主要原因之一。基于纳米技术的基因治疗在最近的癌症治疗临床试验中显示出了显著的治疗益处。最近的研究表明，色素上皮衍生因子（PEDF）蛋白可以通过抗血管生成和促进细胞凋亡来抑制肿瘤生长和转移。在这项研究中，我们使用 iRGD 肽制备了负载 PEDF-DNA 的脂质体，用于转移性 CRC 的癌症靶向基因治疗。我们的结果表明，癌症靶向 PEDF-DNA 脂质体（R-LP/PEDF）在体外显著抑制 CRC 细胞的侵袭、迁移和促凋亡。此外，它减少了肺转移瘤结节，并延长了转移性 CRC 小鼠模型的生存时间。