Exosomes Derived from Human Umbilical Cord Mesenchymal Stem Cells Enhance Cisplatin-induced Apoptotic Effects via the ROS-Fas Pathway in Human NPC-TW01 Nasopharyngeal Carcinoma Cells

Abstract

Background/aim: Although current treatment strategies for nasopharyngeal carcinoma (NPC) have improved, the prognosis for a subset of patients remains poor, largely due to distant metastasis. Resistance to cisplatin is one of the key factors contributing to this unfavorable clinical outcome. This study investigated whether human umbilical cord mesenchymal stem cells-derived exosomes (hUC MSC-Exos) exhibit intrinsic anticancer activity and whether they can enhance the cytotoxic effects of cisplatin in NPC cells.

Materials and methods: The human NPC cell line NPC-TW01 was utilized. Cell viability, protein expression, cytokeratin 18 fragment concentration, mitochondrial membrane potential (MMP) alterations, and reactive oxygen species (ROS) generation were assessed using MTT assay, immunoblotting, ELISA, MMP assay, and ROS detection assay, respectively.

Results: MTT assay results indicated that treatment with 1×10⁹ particles/ml hUC MSC-Exos slightly reduced the viability of NPC-TW01 cells. Notably, cotreatment with hUC MSC-Exos and 12.5 μg/ml cisplatin significantly enhanced cisplatin-induced cytotoxicity. This combination markedly increased the release of cytokeratin 18 fragments and the expression of cleaved caspase-7, both established markers of apoptosis. Moreover, the combination treatment up-regulated the expression of Fas, cleaved caspase-8, cleaved caspase-9, cleaved caspase-3, and tBid, and induced MMP disruption. In addition, the cotreatment significantly elevated ROS levels. Treatment with the ROS scavenger N-acetylcysteine not only suppressed ROS production but also attenuated the levels of cytokeratin 18 fragments, Fas, cleaved caspase-8, cleaved caspase-9, and cleaved caspase-3 induced by the combined treatment in NPC-TW01 cells.

Conclusion: hUC MSC-Exos enhance cisplatin-induced cytotoxicity in NPC-TW01 cells through ROS-dependent activation of the Fas-associated apoptotic signaling pathway. These results suggest that hUC MSC-Exos may serve as a promising adjuvant to augment the therapeutic efficacy of cisplatin in NPC.

Keywords: Human umbilical cord mesenchymal stem cell-derived exosomes; apoptosis; cisplatin; nasopharyngeal carcinoma cells; reactive oxygen species.