3D-cultured adipose tissue-derived stem cells inhibit liver cancer cell migration and invasion through suppressing epithelial-mesenchymal transition.

Abstract

Adipose tissue-derived stem cells (ADSCs) are considered promising candidates for stem cell therapy; however, the tumorigenicity of ADSCs remains controversial. The present study aimed to investigate the association between ADSCs and liver cancer cells, and to determine whether culture methods could influence the effects of ADSCs on liver cancer cell growth in vitro. Liver cancer cells were treated with ADSCs-conditioned medium (CM) that was collected using the two-dimensional (2D) culture method, sphere culture method, or three-dimensional (3D) culture method. After that, cell viability and apoptosis were measured using CCK-8 and Annexin V-FITC assay, respectively; the cell motility and adhesive capacity were analyzed by scratch wound healing and cell adhesion assay, respectively; the cell migration and invasion were examined by Transwell units; and the molecular mechanisms of ADSCs on effecting epithelial mesenchymal transition signaling pathway were further analyzed. The results demonstrated that ADSCs-CM was able to inhibit the growth of liver cancer cells by inhibiting cell proliferation and promoting cell apoptosis, as well as by suppressing cell motility, adhesive capacity, migration and invasion. In addition, ADSCs-CM was able to suppress cell growth via the downregulation of epithelial-mesenchymal transition signaling. Notably, the enhanced inhibitory effects of ADSCs on liver cancer cell growth could be achieved after cultu ring using a 3D approach. These findings suggested that ADSCs may provide a novel promising therapeutic approach for the treatment of patients with liver cancer, and the 3D culture method may provide a novel approach to explore the association between ADSCs and cancer.