Synergistic enhancement of anticancer effects by periodontal ligament stem cell exosomes and oxaliplatin via apoptosis induction and protein modulation

Abstract

Colorectal and oral cancers present significant global health challenges, with conventional treatments often limited by resistance and toxicity. Exosomes, particularly those derived from periodontal ligament stem cells (PDLSCs), offer promising anti-inflammatory, anti-angiogenic, and drug delivery properties. This study aims to investigate the potential of PDLSCs-derived exosomes in enhancing the anticancer efficacy of oxaliplatin on colorectal (HT-29, HCT-116) and oral squamous cell carcinoma (SCC-25) models. PDLSCs-derived exosomes were characterized via nanoparticle tracking analysis, transmission electron microscopy, and flow cytometry, confirming their typical size (80–220 nm), cup-shaped morphology, and expression of surface markers CD9, CD63, and CD81. PKH67-labeling demonstrated efficient exosome internalization by all cancer cell lines. Functional assays showed that PDLSCs-exosomes significantly inhibited cancer cell growth and colony formation in a dose-dependent manner. Synergistic effects were observed when combined with oxaliplatin, enhancing growth inhibition, apoptosis induction, and motility reduction. Apoptotic assays revealed increased gene expression of Bax and p53, with no significant effect on Bcl-2 expression. Proteomic profiling further identified differentially expressed proteins associated with apoptosis, immune signaling, translation, and vesicle fusion. These findings suggest that PDLSCs-exosomes potentiate oxaliplatin activity and sensitize cancer cells to chemotherapy. This study highlights a novel combinatorial approach utilizing stem cell-derived exosomes to augment conventional chemotherapy, offering a promising strategy to mitigate chemoresistance and enhance therapeutic efficacy in colorectal and oral cancers.