Synergistic Inhibitory Effect of Human Umbilical Cord Matrix Mesenchymal Stem Cells-Conditioned Medium and Atorvastatin on MCF7 Cancer Cells Viablity and Migration
Abstract Background: Tumor growth and metastasis eventuate from an interaction between cancer cells and the surrounding extracellular matrix. Recent studies demonstrated inhibitory effects of mesenchymal stem cells on breast tumors. Likewise, the emerging interest in statins as anticancer agents is based on their pleiotropic effects. In the present study, we investigated whether atorvastatin and umbilical cord matrix derived mesenchymal stem cells-conditioned medium alone and combined with each other affect the MCF7 cancer cells viability and interactions.Methods: We measured the viability, apoptosis, and necrosis of MCF7 by MTT assay, Annexin-V/PI staining by flow cytometry, and quantitative real-time PCR. Two-dimensional culture and hanging drop aggregation assay illustrated the morphological changes in single cancer cells and spheroid configuration respectively. We traced the MCF7 migration via scratch-wound healing and trans-well assays. Results: The results showed inhibition of cancer cell viability in all treated groups compared with the control group, but the effect of atorvastatin and conditioned medium combination was further than each one alone. Cancer cells shrinkage and chromatin condensation in the inverted light microscopy and fluorescent staining microscopy indicated apoptosis in treated cells. The annexin V/PI analysis especially in the combination-treated group displayed decreasing in DNA synthesis and cell cycle arrest. The mRNA expressions of caspases 3, 8, 9, and Bcl-2 genes were along with extrinsic and intrinsic apoptosis pathways. Conditioned medium disrupts the connections between cancer cells in the three-dimensional spheroids configuration. The migration of treated cells across the wound area and trans-well diminished, particularly in the combination-treated group. Conclusions: For the first time, the synergistic anti-proliferative and anti-motility effect of atorvastatin along with human umbilical cord mesenchymal stem cells-derived conditioned medium on MCF7 breast cancer cells have been proved. These findings point to some new therapeutic strategies with a focus on the crosstalk between breast cancer cells and microenvironment.