103P P53 Gene Therapy of Human Breast Carcinoma Using a Cationic Non - Viral Vector, Luminescent Silica Nanoparticles

Abstract

ABSTRACT Mutations in the p53 tumor suppressor gene are the most common genetic abnormalities to be described in breast cancer. A new formulation of luminescent silica nanoparticles (LSNs) for gene delivery was produced by the two-step method with slight modification. Plasmid DNA (pp53-EGFP)/LSNs complexes were transfected into human breast cancer cells (MCF-7) and transfection efficiency was determined by FACS analysis. The gene expression was determined by RT-PCR and Western blot analysis. The cellular growth inhibition and apoptosis of treated cells were assessed by trypan blue exclusion assay and annexin V staining, respectively. In vivo biodistribution of plasmid DNA was investigated by PCR and RT-PCR. The transfection efficiency of LSNs showed the highest transfection efficiency among the LSN formulation was higher than that of commercially available Lipofectin®. The LSNs-mediated transfection of the p53 gene resulted in efficient high level of wild-type p53 mRNA and protein expression levels in MCF-7 cells. The efficient reestablishment of wild-type p53 function in breast cancer cells restored the apoptotic pathway. Taken together, our results reveal that cationic LSN-mediated p53 gene delivery may have potential for clinical application as a nonviral vector-mediated breast cancer therapy due to its effective induction of apoptosis and tumor growth inhibition. Disclosure All authors have declared no conflicts of interest.