biostudies-literatureMolika PThe research was financially supported by the National Science, Research and Innovation Fund (NSRF) and Prince of Songkla Universitythe Postdoctoral Fellowship program from the Faculty of Medicine, Prince of Songkla Universitythe Postdoctoral Fellowship program from the Faculty of Medicine, Prince of Songkla University1575https://www.ebi.ac.uk/biostudies/studies/S-EPMC12898660biostudies-literatureUnknown27(3)Cervical cancer (CC) remains a major global health challenge due to chemotherapy resistance and recurrence. Mesenchymal stem cell-derived exosomes (MSC-exosomes) have dual roles, as they can act as therapeutic agents and contribute to chemoresistance. However, their role in response to chemotherapy in CC remains unclear. Therefore, our study investigated the effects of MSC-exosome pretreatment on chemotherapy sensitivity using three-dimensional spheroid models generated from HeLa and SiHa CC cell lines. Proteomic profiling of MSC-exosomes identified key proteins, including ANXA1, ANXA2, EEF2, LGALS1, and PKM2, associated with tumor regeneration and chemotherapy response. MSC-exosomes exhibited context-dependent effects in both chemoresistance and chemosensitization by modulating drug effluInternational journal of molecular sciencesMesenchymal Stem Cell-Derived Exosomes Reprogram Chemosensitivity Pathways in Cervical Cancer Spheroids.PMC12898660MED6801043Sto KN and KKNittayaboon KNavakanitworakul RMolika PKerdkumthong KfalseMesenchymal Stem Cell-Derived Exosomes Reprogram Chemosensitivity Pathways in Cervical Cancer Spheroids.Cervical cancer (CC) remains a major global health challenge due to chemotherapy resistance and recurrence. Mesenchymal stem cell-derived exosomes (MSC-exosomes) have dual roles, as they can act as therapeutic agents and contribute to chemoresistance. However, their role in response to chemotherapy in CC remains unclear. Therefore, our study investigated the effects of MSC-exosome pretreatment on chemotherapy sensitivity using three-dimensional spheroid models generated from HeLa and SiHa CC cell lines. Proteomic profiling of MSC-exosomes identified key proteins, including ANXA1, ANXA2, EEF2, LGALS1, and PKM2, associated with tumor regeneration and chemotherapy response. MSC-exosomes exhibited context-dependent effects in both chemoresistance and chemosensitization by modulating drug efflu2026-01-01T00:00:00Z2026 Feb2026-07-07T03:13:08.953Z2026-07-07T03:08:33.47ZS-EPMC128986604168399310.3390/ijms27031575