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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\u2010only (Control); (b) A2058 and ESCs continuously co\u2010cultured (Group One); (c) A2058 co\u2010cultured with daily refreshed ESCs (Group two); (d) Group one with VO\u2010Ohpic, inhibitor of PTEN (VO\u2010Ohpic 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\u2010regulation of PI3K\/AKT pathway. Besides, the above mentioned anti\u2010tumor effects on A2058 cells were significantly enhanced in group two but statistically weakened after administration of VO\u2010Ohpic compared to group one. We demonstrate that ESC microenvironment reduces the malignancy of A2058 by down\u2010regulating PI3K\/AKT pathway. Notably, such anti\u2010tumor effects can be enhanced by appropriately increasing the quality and quantity of ESCs in co\u2010culture system. Our results suggest that ESC microenvironment could be an effective and safe approach to treating cancer.<\/jats:p>","DOI":"10.1002\/cam4.2207","type":"journal-article","created":{"date-parts":[[2019,6,7]],"date-time":"2019-06-07T09:34:06Z","timestamp":1559900046000},"page":"4265-4277","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Embryonic stem cell microenvironment suppresses the malignancy of cutaneous melanoma cells by down\u2010regulating PI3K\/AKT pathway"],"prefix":"10.1002","volume":"8","author":[{"given":"Chenjie","family":"Wang","sequence":"first","affiliation":[{"name":"State Key Laboratory of Ophthalmology Zhongshan Ophthalmic Center, Sun Yat\u2010sen University Guangzhou  510060 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoran","family":"Wang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Ophthalmology Zhongshan Ophthalmic Center, Sun 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