Zinc Oxide Nanoparticles Modulate PBMC Cytokines and Trigger Cytotoxicity, Apoptosis, and Anti-angiogenic Effects in HeLa Cells in Co-culture
Abstract
Cervical cancer is the fourth most prevalent malignancy among women globally. Zinc oxide nanoparticles (ZnO-NPs) possess significant potential in cancer therapy due to their unique physicochemical properties, biocompatibility, and apoptosis-inducing abilities. While ZnO-NPs have been examined in HeLa cells and peripheral blood mononuclear cells (PBMCs) individually, their immunological and angiogenesis-related effects in immune-tumor co-culture systems was insufficiently investigated. This study assessed the apoptotic, anti-angiogenic, and cytokine-modulating effects of ZnO-NPs in a HeLa/PBMC co-culture model.
HeLa cells were co-cultured with PBMCs and treated with ZnO-NPs under different groups. Cytotoxicity was evaluated using MTT assay, apoptosis was analyzed by flow cytometry, and gene expression levels were measured using real-time PCR.
ZnO-NPs significantly reduced HeLa cells viability with a half maximal inhibitory concentration (IC50) of 7 µg/mL, while PBMCs showed more resistance (IC50=40 µg/mL). In the HeLa/PBMC/ZnO co-culture group, gene expression analysis in PBMCs revealed significant upregulation of IL1B, TNF, IFNG, and TGFB1 compared with the HeLa/PBMC group, while IL2 and IL4 expression levels showed no significant changes. VEGFA expression in HeLa cells was reduced in all treated groups, with the greatest decrease in the HeLa/PBMC/ZnO group. Co-culture with PBMCs and ZnO-NP treatment significantly promoted apoptosis in HeLa cells.
In conclusion, ZnO-NPs induce cytotoxic and anti-angiogenic effects on HeLa cells, particularly within a PBMC co-culture setting, highlighting the contribution of immune–tumor interactions to ZnO-NP–mediated anti-cancer responses; however, more investigations at the protein and functional levels are necessary to validate these effects.
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| Keywords | ||
| Cervical cancer Co-culture technique HeLa cells Nanoparticles Zinc oxide | ||
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