Regulation of Interferon-β-Modified Human Umbilical Cord Mesenchymal Stem Cell-Derived Exosomes in Proliferation and Apoptosis of Prostate Cancer Cells

Organogenesis. 2023 Dec 31;19(1):2285836. doi: 10.1080/15476278.2023.2285836. Epub 2023 Nov 30.

Abstract

Prostate cancer (PCa) poses a serious burden to men. Interferon-β (IFN-β) is implicated in cancer cell growth. This study hence explored the regulation of IFN-β-modified human umbilical cord mesenchymal stem cell-derived exosomes (hUCMSC-Exos) in PCa cells. In vitro-cultured hUCMSCs were transfected with pcDNA3.1-IFN-β plasmid or IFN-β siRNA. hUCMSC-Exos were extracted by ultracentrifugation and identified. PCa cells (PC3 and LNCap) were treated with Exos. Cellular internalization of Exos by cells was detected by uptake assay. Cell proliferation, cycle, and apoptosis were evaluated by CCK-8, EdU staining, and flow cytometry. Levels of cell cycle-related proteins (cyclin D/cyclin E) were determined by Western blot. The effect of IFN-β-modified hUCMSC-Exos in vivo was analyzed. IFN-β-modified hUCMSC-Exos (Exooe-IFN or Exosi-IFN) were successfully isolated. IFN-β was encapsulated in Exos, and PCa cells could uptake Exos. After treating with Exooe-IFN, PCa cell proliferation was impeded, the percentage of cells in the G0/G1 phase, cyclin D/cyclin E levels, and cell apoptotic rate were elevated, while cells treated with Exooe-IFN exhibited contrary trends. IFN-β-modified hUCMSC-Exos reduced PCa tumor size and weight in vivo. Conjointly, IFN-β-modified hUCMSC-Exos suppress PCa cell proliferation and facilitate apoptosis.

Keywords: Apoptosis; PC3 cells; cell cycle; human umbilical cord mesenchymal stem cell-derived exosomes; interferon-β; proliferation; prostate cancer.

MeSH terms

  • Apoptosis / genetics
  • Cell Proliferation
  • Cyclin D / metabolism
  • Cyclin E / metabolism
  • Exosomes* / genetics
  • Exosomes* / metabolism
  • Humans
  • Immunologic Factors / metabolism
  • Interferon-beta / metabolism
  • Male
  • Mesenchymal Stem Cells*
  • Prostatic Neoplasms* / metabolism
  • Umbilical Cord / metabolism

Substances

  • Cyclin E
  • Interferon-beta
  • Immunologic Factors
  • Cyclin D

Grants and funding

This work was supported by Research Foundation of Peking University Shenzhen Hospital (Grant no.JCYJ2021013) and The Health and Family Planning Commision of Shenzhen (Grant no. SZBC2017021).