How mesenchymal stem cell conditioned media affect the HeLa cells on Wnt/beta-catenin signaling, Notch-1 signaling, and apoptosis?

Abstract

This study aims to investigate the influence of mesenchymal stem cells (MSCs) cell-conditioned media (MSCs-CM) on the Wnt/beta-catenin and Notch-1 signaling as well as the apoptosis in cervical cancer cells. Conditioned media of characterized MSCs were freshly collected and filtered before use. HeLa cells cultured standard conditions and treated with MSCs-CM 24, 48, 72 hours. Untreated cells serve as a control. Cell viability measured with MTT assay for all incubation periods. Immunocytochemical staining of beta-catenin, Notch-1 and cleaved caspase 3 were performed for each time-point. MTT cell viability, AO/PI, and immunocytochemical staining of cleaved caspase 3 results showed that through all incubation periods, there was no statistically significant difference between the MSCs-CM treated HeLa cells and the controls (p>0.05). Beta-catenin immunoreactivity was upregulated following treatment from 24 hours to 48 and 72 hours (p<0.001), however a significant decrease in Notch-1 receptor expression after MSCs-CM treatment independent of time (p<0.001). This study demonstrated that MSCs-CM has no cytotoxic and proliferative effects on HeLa cells. However, treatment with MSCs-CM enhanced the activity of Wnt/beta-catenin signaling via the accumulation of beta-catenin and decreased Notch-1 signaling in HeLa cells. Further analyses that identify regulatory factors of these pathways may provide promising opportunities for cervical cancer therapy.

Keywords

• Mesenchymal stem cell
• Beta-catenin
• Notch-1
• Cancer therapy

References

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