Transfection with p21 and p53 tumor suppressor plasmids suppressed breast tumor growth in syngeneic mouse model

Nabilah Ibnat1, Nur Izyani Kamaruzman1, Maeirah Ashaie1

  • 1Faculty of Medicine, Nursing and Health Sciences, Monash University, Australia.

Gene
|March 23, 2019
PubMed

Insights

This study shows that delivering tumor suppressor plasmids p21 and p53 using nanoparticles effectively reduces breast cancer cell growth. In vivo studies confirmed significant tumor volume reduction in mice treated with these nanoparticle-delivered gene therapies.

Area of Science:

  • Oncology
  • Nanotechnology
  • Molecular Biology

Background:

  • Gene therapy offers a promising avenue for breast cancer treatment.
  • Tumor suppressor genes like p21 and p53 play crucial roles in cell cycle regulation and apoptosis.
  • Effective delivery of therapeutic plasmids to cancer cells remains a challenge.

Purpose of the Study:

  • To evaluate the efficacy of inorganic carbonate apatite nanoparticles (NPs) for delivering p21 and p53 tumor suppressor plasmids into breast cancer cells.
  • To assess the impact of combined p21 and p53 gene delivery on breast cancer cell proliferation and tumor growth in vitro and in vivo.

Main Methods:

  • Transfection of p21 and p53 tumor suppressor plasmids into breast cancer cell lines (MDA-MB-231, MCF-7, 4T1) using carbonate apatite nanoparticles.
  • Cytotoxicity assays to measure cell growth inhibition.
  • Western blot analysis to examine the expression of MAPK/ERK pathway proteins.
  • In vivo studies using a syngeneic breast cancer mouse model to evaluate tumor growth reduction.

Main Results:

  • Combined delivery of p21 and p53 plasmids via NPs significantly reduced cell growth in MDA-MB-231 cells compared to single gene delivery.
  • Significant reduction in cellular growth was observed in MCF-7 and 4T1 cell lines following p21 or p53 plasmid transfection.
  • NP-mediated delivery of p21 and p53 suppressed the phosphorylated form of MAPK protein in MDA-MB-231 cells.
  • Intravenous injection of p21 + NP and p53 + NP therapeutics led to a greater reduction in tumor growth rate and final tumor volume in mice.

Conclusions:

  • Carbonate apatite nanoparticles are effective carriers for delivering tumor suppressor plasmids p21 and p53 in breast cancer treatment.
  • Combined gene therapy with p21 and p53 shows enhanced efficacy in reducing breast cancer cell proliferation and tumor growth.
  • This nanoparticle-mediated gene delivery approach holds potential for developing novel breast cancer therapeutics.

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