An enhanced anti-tumor effect of apoptin-cecropin B on human hepatoma cells by using bacterial magnetic particle gene delivery system

Biochem Biophys Res Commun. 2018 Feb 5;496(2):719-725. doi: 10.1016/j.bbrc.2018.01.108.

Abstract

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.

Keywords: Bacterial magnetic particles; Gene therapy; Hepatocellular carcinoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / metabolism
  • Capsid Proteins / genetics*
  • Carcinoma, Hepatocellular / genetics
  • Carcinoma, Hepatocellular / pathology
  • Carcinoma, Hepatocellular / therapy*
  • Drug Carriers / chemistry
  • Female
  • Gene Transfer Techniques*
  • Genetic Therapy / methods
  • Genetic Vectors / administration & dosage*
  • Genetic Vectors / genetics
  • Genetic Vectors / therapeutic use
  • Hep G2 Cells
  • Humans
  • Insect Proteins / genetics*
  • Liver Neoplasms / genetics
  • Liver Neoplasms / pathology
  • Liver Neoplasms / therapy*
  • Magnetosomes / chemistry*
  • Magnetospirillum / chemistry*
  • Mice, Inbred BALB C
  • Mice, Nude
  • Transfection / methods

Substances

  • Antineoplastic Agents
  • Capsid Proteins
  • Drug Carriers
  • Insect Proteins
  • VP3 protein, Chicken anemia virus
  • cecropin B protein, Insecta