CELL INTELLIGENCE · 肿瘤细胞治疗研究

Ovarian cancer is the most lethal gynecologic malignancy, with chemoresistance and recurrence driven by cancer stem cells (CSCs). Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) mediate tumor-stroma communication, but their role in ovarian cancer progression and therapy remains unclear. Here, we investigated bone marrow (BM)-MSC-EVs, their effects on ovarian cancer cells, and the underlying molecular mechanisms. BM-MSCs were isolated, confirmed using flow cytometry and trilineage differentiation, and their EVs characterized using nanoparticle tracking analysis, transmission electron microscopy, and Western blotting. Kuramochi cells were treated with BM-MSC-EVs and assessed for proliferation, colony formation, migration, invasion, apoptosis, and chemosensitivity. Aldehyde dehydrogenase (ALDH + ) Kuramochi cells, with or without EV exposure, were transplanted into non-obese diabetic severe combined immunodeficiency mice for xenograft studies, followed by histology, immunohistochemistry, Western blotting, and EV miRNA profiling. BM-MSC-EVs increased cancer cell proliferation but reduced colony formation, migration, and invasion in vitro. They sensitized ALDH + CSC-like cells to carboplatin, while paclitaxel response remained unchanged. In vivo, EVs accelerated tumor growth and activated prosurvival (p-AKT, BCL-2), angiogenic (VEGFA, CD31), and epithelial-mesenchymal transition-associated (vimentin) pathways. EVs were found to be enriched in hsa-miR-100-5p, hsa-miR-122-5p, and hsa-let-7i-5p based on miRNA array analysis, and these findings were further validated by qRT-PCR. These findings reveal the dual roles of BM-MSC-EVs: enhancing carboplatin sensitivity while promoting tumor progression and angiogenesis.