School of Life Science, Sichuan University, Chengdu, PR China.
Oncol Rep. 2010 Sep;24(3):661-8. doi: 10.3892/or_00000905.
Colon carcinoma is one of the common malignant tumors and has high morbidity and mortality in the world. Pigment epithelial-derived factor (PEDF) has been found to be the most potent natural inhibitor of angiogenesis and PEDF gene has been extensively used for the therapy of tumors, which suggests a potential approach to the therapy of colon carcinoma. However, the transfer of PEDF gene largely depends on the effective gene delivery systems. Poly (lactic-co-glycolic acid) nanoparticles (PLGANPs) have been extensively used for gene therapy due to its low-toxicity, biocompatibility and biodegradability, due to its potential to be an excellent carrier of the PEDF gene. We investigated the effect of PEDF gene loaded in PLGA nanoparticles (PEDF-PLGANPs) on the mouse colon carcinoma cells (CT26s) in vitro and in vivo. Blank PLGANPs (bPLGANPs) showed lower cytotoxicity than PEI to the CT26s. In vitro, PEDF-PLGANPs directly induced CT26 apoptosis and inhibit human umbilical vein endothelial cell (HUVEC) proliferation. In vivo, PEDF-PLGANPs inhibited CT26 tumors growth by inducing CT26 apoptosis, decreasing MVD and inhibiting angiogenesis. Our present study demonstrates the inhibitory effect of PEDF-PLGANPs on the growth of CT26s in vitro and in vivo for the first time. PLGANP-mediated PEDF gene could provide an innovative strategy for the therapy of colon carcinoma.
结肠癌是常见的恶性肿瘤之一，在世界范围内具有较高的发病率和死亡率。色素上皮衍生因子（PEDF）已被发现是最强的天然血管生成抑制剂，PEDF 基因已广泛用于肿瘤治疗，这为结肠癌的治疗提供了一种潜在的方法。然而，PEDF 基因的转移在很大程度上依赖于有效的基因传递系统。聚（乳酸-共-乙醇酸）纳米粒（PLGANPs）由于其低毒性、生物相容性和可生物降解性，已被广泛用于基因治疗，因为它有可能成为 PEDF 基因的优秀载体。我们研究了载有 PEDF 基因的 PLGA 纳米粒（PEDF-PLGANPs）对体外和体内小鼠结肠癌细胞（CT26）的影响。空白 PLGANPs（bPLGANPs）对 CT26 的细胞毒性低于 PEI。体外，PEDF-PLGANPs 直接诱导 CT26 细胞凋亡并抑制人脐静脉内皮细胞（HUVEC）增殖。体内，PEDF-PLGANPs 通过诱导 CT26 细胞凋亡、减少 MVD 和抑制血管生成来抑制 CT26 肿瘤的生长。本研究首次证明了 PEDF-PLGANPs 对 CT26s 体内外生长的抑制作用。PLGANP 介导的 PEDF 基因可能为结肠癌的治疗提供一种创新策略。
