Department of Clinical Genetics and Experimental Medicine, Fuzong Clinical College, Fujian Medical University, Fuzhou, Fujian 350025, P.R. China.
The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, Fujian 350025, P.R. China.
Int J Mol Med. 2018 Mar;41(3):1385-1396. doi: 10.3892/ijmm.2017.3336. Epub 2017 Dec 20.
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.
脂肪组织来源的干细胞（ADSCs）被认为是干细胞治疗的有前途的候选者；然而，ADSCs 的致瘤性仍存在争议。本研究旨在探讨 ADSCs 与肝癌细胞之间的关系，并确定培养方法是否会影响 ADSCs 对肝癌细胞体外生长的影响。用二维（2D）培养法、球体培养法或三维（3D）培养法收集 ADSCs 条件培养基（CM）处理肝癌细胞。然后，通过 CCK-8 和 Annexin V-FITC 检测分别测量细胞活力和细胞凋亡；通过划痕愈合和细胞黏附检测分别分析细胞迁移和黏附能力；通过 Transwell 小室检测细胞迁移和侵袭；并进一步分析 ADSCs 对上皮间质转化信号通路的影响机制。结果表明，ADSCs-CM 通过抑制细胞增殖和促进细胞凋亡，以及抑制细胞迁移、黏附和侵袭，抑制肝癌细胞的生长。此外，ADSCs-CM 通过下调上皮间质转化信号通路抑制细胞生长。值得注意的是，3D 培养方法可增强 ADSCs 对肝癌细胞生长的抑制作用。这些发现表明，ADSCs 可能为肝癌患者的治疗提供一种新的有前途的治疗方法，3D 培养方法可能为探索 ADSCs 与癌症之间的关系提供一种新的方法。
