Malignant cancer cells engage in a dynamic reciprocity with the tumor microenvironment (TME) that promotes tumor growth, development, and resistance to therapy. Early embryonic blastocyst microenvironments can reverse the tumorigenic phenotype of malignant cancer cells via ameliorating of TME. It is potential to apply embryonic stem cell (ESC) microenvironment to suppress the malignant behaviors of cancer cells. This study aimed to investigate a better method and the mechanism of ESC microenvironment supplied by ESCs on suppressing the malignancy of cutaneous melanoma cells. Cutaneous melanoma cell line A2058 were cultured and divided into four groups: (a) A2058-only (Control); (b) A2058 and ESCs continuously co-cultured (Group One); (c) A2058 co-cultured with daily refreshed ESCs (Group two); (d) Group one with VO-Ohpic, inhibitor of PTEN (VO-Ohpic Group). The results showed that, compared to control group, A2058 cells in group one exhibited decreased cellular proliferation, migration, invasiveness and vasculogenic mimicry concomitant with an increase in cell apoptosis, accompanied by down-regulation of PI3K/AKT pathway. Besides, the above mentioned anti-tumor effects on A2058 cells were significantly enhanced in group two but statistically weakened after administration of VO-Ohpic compared to group one. We demonstrate that ESC microenvironment reduces the malignancy of A2058 by down-regulating PI3K/AKT pathway. Notably, such anti-tumor effects can be enhanced by appropriately increasing the quality and quantity of ESCs in co-culture system. Our results suggest that ESC microenvironment could be an effective and safe approach to treating cancer.
Keywords: PI3K/AKT; anti-tumor effects; embryonic stem cell; melanoma; microenvironment.
© 2019 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.