Human bone marrow mesenchymal stem cell-derived exosomes (BMSCs-Exos) have shown potential as an effective therapeutic tool for the management of colorectal cancer (CRC). Aberrant Wnt pathway activation has been established as a primary mechanism that drives CRC progression. This study aimed to evaluate the potential efficacy of BMSCs-Exos in CRC cell proliferation, migration, and invasion via modulation of the Wnt pathway in vitro. Exos were isolated from the supernatant of cultured human BMSCs and characterized using transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), and Western blotting. BMSCs-Exos were introduced to human CRC cell lines (HCT116 and SW480) to detect the effects of BMSCs-Exos on CRC cell proliferation, invasion, migration, and apoptosis by CCK-8, Transwell, and flow cytometric assays. Furthermore, the potential mechanism of BMSCs-Exos in regulating these functions of HCT116 and SW480 cells was investigated by quantitative reverse transcription-PCR (RT-qPCR) and Western blotting for the expression levels of the Wnt pathway-related genes. BMSCs-Exo treatment decreased HCT116 and SW480 cell proliferation, migration, and invasion, and potentiated apoptosis of CRC cells. Moreover, mRNA and protein expression patterns of the Wnt pathway-related genes Wnt1, Wnt2, Wnt3, and Wnt3a, as well as protein expression of nuclear β-catenin, were downregulated in HCT116 and SW480 cells after treatment with BMSCs-Exos. Conversely, the activated Wnt pathway partially offset the regulatory effects of BMSCs-Exos on HCT116 and SW480 cell malignant behaviors and nuclear β-catenin protein expression. These findings suggest that BMSCs-Exos repress the Wnt pathway with subsequent reduction of β-catenin nuclear translocation, promoting cell apoptosis and thereby attenuating proliferation, migration, and invasion of CRC cells in vitro.
Jingyi Fan (Tue,) studied this question.