Human Umbilical Cord Mesenchymal Stem Cells Inhibit the Development of Cervical Cancer in Vitro and in Vivo, and Affect Signal Transduction of the Wnt/β-Catenin/c-Myc Axis

Jin Yang, Wenfeng Zhang, Qing Liu, Na Yu, Xueyun Liu

Article ID: 7696
Vol 37, Issue 12, 2023
DOI: https://doi.org/10.23812/j.biol.regul.homeost.agents.20233712.640
Received: 8 January 2024; Accepted: 8 January 2024; Available online: 8 January 2024; Issue release: 8 January 2024

Abstract

Background: Cervical cancer (CC) is a common malignant tumor in women, ranking fourth in terms of both incidence and mortality. It is often diagnosed in the intermediate or advanced stages and has an extremely low complete cure rate. Human umbilical cord mesenchymal stem cells (hUCMSCs) have been found to have anti-tumor potential. Therefore, we aimed to investigate the role of hUCMSCs in the occurrence and development of CC and the underlying mechanisms. Methods: Initially, the in vitro effects of mesenchymal stem cells (MSCs) supernatant and the MSCs + HeLa cells co-culture on the viability, migration, invasion, and apoptosis of HeLa cells were determined. A CC mouse model was successfully established. Then, the model mouse was administered with MSCs to assess the role of MSCs on the growth of CC tumors. Furthermore, the expression levels of proteins associated with the Wnt/β-Catenin/c-Myc signaling pathway were evaluated in tumor tissues using Western blot analysis. Additionally, the levels of inflammatory cytokines were measured in peripheral blood samples using their respective enzyme-linked immunosorbent assay (ELISA) detection kits. Results: Through in vitro experimental settings, it was found that MSCs supernatant significantly suppressed the viability and metastasis of HeLa cells while inducing the apoptosis of HeLa cells compared with HeLa cells cultured alone (p < 0.05). However, when HeLa cells were co-cultured with MSCs, there was no significant inhibitory or promoting effect on HeLa cells. Furthermore, in the in vivo experiments, compared to the control group, the injection of MSCs significantly suppressed the growth of CC cells in vivo, induced apoptosis in these cells, suppressed the expression of β-Catenin and c-Myc proteins, increased the expression of glycogen synthase kinase-3β (GSK-3β), upregulated the levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interferon-γ (IFN-γ), and downregulated the level of transforming growth factor-β (TGF-β) (p < 0.05). Conclusion: hUCMSCs can significantly inhibit the occurrence and development of CC, concurrently suppress the Wnt/β-Catenin/c-Myc signaling pathway, and subsequently regulate the secretion of inflammatory cytokines.


Keywords

hUCMSCs;cervical cancer;HeLa cells;Wnt/β-Catenin/c-Myc axis


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