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

Organogenesis(2023)

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摘要
Prostate cancer (PCa) poses a serious burden to men. Interferon-beta (IFN-beta) is implicated in cancer cell growth. This study hence explored the regulation of IFN-beta-modified human umbilical cord mesenchymal stem cell-derived exosomes (hUCMSC-Exos) in PCa cells. In vitro-cultured hUCMSCs were transfected with pcDNA3.1-IFN-beta plasmid or IFN-beta 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-beta-modified hUCMSC-Exos in vivo was analyzed. IFN-beta-modified hUCMSC-Exos (Exo(oe-)(IFN)(-beta) or Exo(si-)(IFN)(-beta)) were successfully isolated. IFN-beta was encapsulated in Exos, and PCa cells could uptake Exos. After treating with Exo(oe-)(IFN)(-beta), 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 Exo(oe-)(IFN)(-beta) exhibited contrary trends. IFN-beta-modified hUCMSC-Exos reduced PCa tumor size and weight in vivo. Conjointly, IFN-beta-modified hUCMSC-Exos suppress PCa cell proliferation and facilitate apoptosis.
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关键词
Apoptosis,cell cycle,human umbilical cord mesenchymal stem cell-derived exosomes,interferon-beta,PC3 cells,proliferation,prostate cancer
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