Nanoliposome-mediated FL/TRAIL double-gene therapy for colon cancer: in vitro and in vivo evaluation

Cancer Lett. 2012 Feb 1;315(1):69-77. doi: 10.1016/j.canlet.2011.10.010. Epub 2011 Oct 18.

Abstract

Objective: To investigate the therapeutic effects of cationic nanoliposome-mediated gene therapy combined with immunotherapy for colon cancer treatment.

Methods: Recombinant plasmids containing green and red fluorescent protein reporter genes were constructed using gene cloning methods. Gene-carrying cationic nanoliposomes were prepared based on the electrostatic adherence principle and then transfected into dendritic cells (DC), which were transplanted into colon cancer cells.

Results: Recombinant plasmids containing green or red fluorescent protein reporter genes were successfully constructed by gene cloning and confirmed by restriction enzyme digestion and sequencing. Gene-carrying cationic nanoliposomes were transfected into colon cancer cells, and good gene expression was detected. A better level of apoptosis was observed in the combined group of tyrosine kinase receptor 3 ligand (FL) and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), while the lowest level was detected in the control group. The parameters in the FL and TRAIL groups were between the above-mentioned combined group.

Conclusion: Cationic nanoliposomes have the advantage of being gene carriers. The joint therapeutic effects of the two genes are superior to those of a single gene. Gene therapy combined with immunotherapy has significant implications for cancer treatment.

MeSH terms

  • Animals
  • Colonic Neoplasms / genetics*
  • Colonic Neoplasms / immunology
  • Colonic Neoplasms / pathology
  • Colonic Neoplasms / therapy*
  • Dendritic Cells / immunology*
  • Female
  • Genetic Therapy
  • Green Fluorescent Proteins / genetics
  • Humans
  • Immunotherapy, Adoptive
  • Liposomes / administration & dosage
  • Luminescent Proteins / genetics
  • Male
  • Membrane Proteins / genetics*
  • Mice
  • Nanoparticles / administration & dosage
  • Red Fluorescent Protein
  • TNF-Related Apoptosis-Inducing Ligand / genetics*
  • Transfection

Substances

  • Liposomes
  • Luminescent Proteins
  • Membrane Proteins
  • TNF-Related Apoptosis-Inducing Ligand
  • TNFSF10 protein, human
  • flt3 ligand protein
  • Green Fluorescent Proteins