利用细菌磁性颗粒基因递送系统增强凋亡素-天蚕素B对人肝癌细胞的抗肿瘤作用。
An enhanced anti-tumor effect of apoptin-cecropin B on human hepatoma cells by using bacterial magnetic particle gene delivery system.
作者信息
Wang Xi, Wang Ji-Gui, Geng Yuan-Yuan, Wang Jiao-Jiao, Zhang Xiao-Mei, Yang Shuang-Shuang, Jiang Wei, Liu Wei-Quan
机构信息
State Key Laboratories of Agrobiotechnology, College of Biological Sciences, China Agricultural University, PR China.
State Key Laboratories of Agrobiotechnology, College of Biological Sciences, China Agricultural University, PR China.
出版信息
Biochem Biophys Res Commun. 2018 Feb 5;496(2):719-725. doi: 10.1016/j.bbrc.2018.01.108.
The gene therapy of cancer, due to the limit of its efficiency and safety, has not been widely used in clinical. Recently, bacterial magnetic particles (BMPs), which are membrane-bound nanocrystals found in magnetotactic bacteria, have been exploited as a new gene delivery system. However, its application on gene therapy remains to be explored. In our previous study, we found that a combination of cecropin B (ABPs) and apoptin (VP3) could serve as an effective gene therapeutic agent. Thus, in this study, we used BMPs to deliver the co-expression plasmid of these two gene, namely pVAX1-VA, and evaluated its therapeutic effect on human hepatocellular carcinoma (HepG2). Our results showed that BMPs significantly improved the efficiency of gene transfection (almost 3-fold than Lipofectamine 2000 at 48 h, P < .001), which led to stronger apoptosis (in a peak almost 2-fold than Lipofectamine 2000-pVAX1-VA, P < .01) and growth inhibition of HepG2 cells. More importantly, compared with Lipofectamine 2000-pVAX1-VA group, BMP-pVAX1-VA strikingly inhibited tumor growth (0.60 ± 0.09 g vs. 0.88 ± 0.11 g, P < .05) in nude mouse tumor models and increased the tumor-infiltrating lymphocytes considerably without apparent cytotoxicity. These findings suggest that BMPs could be an attractive gene delivery system for gene therapy and provide a potential available treatment for human hepatocellular carcinoma and maybe some other kinds of tumors.
由于癌症基因治疗在效率和安全性方面存在局限性,尚未在临床上广泛应用。最近,细菌磁性颗粒(BMPs),即趋磁细菌中发现的膜结合纳米晶体,已被开发为一种新的基因递送系统。然而,其在基因治疗中的应用仍有待探索。在我们之前的研究中,我们发现天蚕素B(ABPs)和凋亡素(VP3)的组合可以作为一种有效的基因治疗剂。因此,在本研究中,我们使用BMPs递送这两个基因的共表达质粒,即pVAX1-VA,并评估其对人肝癌细胞(HepG2)的治疗效果。我们的结果表明,BMPs显著提高了基因转染效率(48小时时几乎比Lipofectamine 2000高3倍,P<0.001),这导致更强的细胞凋亡(峰值时几乎比Lipofectamine 2000-pVAX1-VA高2倍,P<0.01)和HepG2细胞的生长抑制。更重要的是,与Lipofectamine 2000-pVAX1-VA组相比,BMP-pVAX1-VA在裸鼠肿瘤模型中显著抑制肿瘤生长(0.60±0.09 g对0.88±0.11 g,P<0.05),并显著增加肿瘤浸润淋巴细胞,且无明显细胞毒性。这些发现表明,BMPs可能是一种有吸引力的基因治疗基因递送系统,并为人类肝细胞癌以及可能的其他类型肿瘤提供了一种潜在的有效治疗方法。