A chemoenzymatically synthesized cholesterol-g-poly(amine-co-ester)-mediated p53 gene delivery for achieving antitumor efficacy in prostate cancer

Int J Nanomedicine. 2019 Feb 13:14:1149-1161. doi: 10.2147/IJN.S191905. eCollection 2019.

Abstract

Background: An amphiphilic cationic copolymer cholesterol-g-poly(amine-co-ester), namely Chol-g-PMSC-PPDL synthesized in a chemoenzymatic route has been utilized as a carrier for p53 gene delivery to check its antitumor efficacy, using human prostate cancer cell line PC-3 (p53 null) as a model.

Materials and methods: The transfection efficiency was measured by quantitative PCR and Western blotting assay. The anti-proliferative effect was detected using MTT method, colony formation assay and Live/Dead staining. The anti-migration effect was evaluated through wound healing and Transwell migration assays.

Results: The transfection efficiency assay indicated that the carrier-mediated p53 gene transfection could dramatically enhance the intracellular p53 expression level. Through p53 gene delivery, obvious anti-proliferative effect could be detected which was elucidated to be associated with the simultaneous activation of mitochondrial-dependent apoptosis pathway and cell cycle arrest at G1 phase. Meanwhile, the anti-migration effect could be obtained after p53 gene transfection.

Conclusion: Chol-g-PMSC-PPDL-mediated p53 gene transfection could potentially be employed as a promising strategy for achieving effective anti-tumor response.

Keywords: anti-migration effect; anti-proliferation effect; cholesterol-g-poly(amine-co-ester); gene therapy; p53 gene delivery.

MeSH terms

  • Apoptosis
  • Cell Line, Tumor
  • Cell Proliferation
  • Cell Survival
  • Cholesterol Esters / chemical synthesis*
  • Cholesterol Esters / chemistry
  • Gene Transfer Techniques*
  • Humans
  • Male
  • Nanoparticles / chemistry
  • Prostatic Neoplasms / therapy*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Tumor Suppressor Protein p53 / genetics*
  • Tumor Suppressor Protein p53 / metabolism
  • Tumor Suppressor Protein p53 / therapeutic use*
  • Wound Healing

Substances

  • Cholesterol Esters
  • RNA, Messenger
  • Tumor Suppressor Protein p53