School of Medicine, Jiangsu University, Zhenjiang, Jiangsu 212013, P.R. China.
Laboratory Center, Affiliated People's Hospital of Jiangsu University, Zhenjiang, Jiangsu 212002, P.R. China.
Oncol Rep. 2017 Aug;38(2):1013-1020. doi: 10.3892/or.2017.5729. Epub 2017 Jun 16.
Human embryonic stem cell derived-mesenchymal stem cells (hESC‑MSCs) are able to inhibit proliferation of leukemia cells. Microvesicles released from human embryonic stem cell derived-mesenchymal stem cells (hESC‑MSC‑MVs) might play an important part in antitumor activity. Microvesicles were isolated by ultracentrifugation and identified under a scanning electron microscopy and transmission electron microscope separately. After 48-h cocultured with hESC‑MSCs and hESC‑MSC‑MVs, the number of K562 and HL60 was counted and tumor cell viability was measured by CCK8 assay. The expression of proteins Bcl-2 and Bax were estimated by western blotting. Transmission electron microscope and western blot analysis were adopted to evaluate the autophagy level. Results showed that both hESC‑MSCs and hESC‑MSC‑MVs inhibited proliferation of leukemia cells in a concentration-dependent manner. hESC‑MSC‑MVs reduced the ratio of Bcl/Bax, enhanced the protein level of Beclin-1 and LC3-II conversion, thus upregulating autophagy and apoptosis. In conclusion, microvesicles released from human embryonic stem cell derived-mesenchymal stem cells inhibited tumor growth and stimulated autophagy and excessive autophagy might induce apoptosis.
人胚胎干细胞来源的间充质干细胞（hESC-MSCs）能够抑制白血病细胞的增殖。人胚胎干细胞来源的间充质干细胞（hESC-MSC-MVs）释放的微囊泡可能在抗肿瘤活性中发挥重要作用。通过超速离心分离微囊泡，并分别在扫描电子显微镜和透射电子显微镜下进行鉴定。与 hESC-MSCs 和 hESC-MSC-MVs 共培养 48 小时后，用 CCK8 法计数 K562 和 HL60 的数量，并通过 CCK8 法测量肿瘤细胞活力。通过 Western blot 测定蛋白 Bcl-2 和 Bax 的表达。采用透射电子显微镜和 Western blot 分析来评估自噬水平。结果表明，hESC-MSCs 和 hESC-MSC-MVs 均呈浓度依赖性抑制白血病细胞增殖。hESC-MSC-MVs 降低了 Bcl/Bax 比值，增强了 Beclin-1 蛋白水平和 LC3-II 转化，从而上调自噬和细胞凋亡。综上所述，人胚胎干细胞来源的间充质干细胞释放的微囊泡抑制肿瘤生长并刺激自噬，过度自噬可能诱导细胞凋亡。
