Transforming growth factor beta (TGF-β) is a multifunctional cytokine with important functions in cell proliferation and differentiation. TGF-β is highly expressed in several types of cancers and promotes tumor invasion and metastasis. However, the role of TGF-β in osteosarcoma progression is poorly understood. In the present study, we found that TGF-β is highly expressed in osteosarcoma cells and tissues, and is associated with high Ennecking stage (P = 0.033), metastasis, and recurrence. TGF-β-knockdown osteosarcoma cell lines were established using siRNA (si-TGF-β). Cells transfected with si-TGF-β exhibited significantly reduced proliferation, migration/invasion, and colony formation abilities, and increased levels of cell apoptosis. In addition, si-TGF-β treatment reduced spheroid size, the ratio of CD133-positive cells, and expression of SOX-2, Nanog, and Oct-3/4 in osteosarcoma cells. Mechanistically, PI3K/mTOR phosphorylation is inhibited by TGF-β knockdown. Pretreatment with 25 µM LY294002, a PI3K-specific inhibitor, further enhanced the si-TGF-β-induced suppression of osteosarcoma progression. Taken together, these results reveal a novel role for TGF-β in osteosarcoma progression and modulation of stemness-related traits and indicate that TGF-β may be of value as a therapeutic target for the treatment of osteosarcoma.

转化生长因子β（TGF-β）是一种多功能细胞因子，在细胞增殖和分化中具有重要功能。TGF-β在几种类型的癌症中高度表达，并促进肿瘤的侵袭和转移。然而，人们对TGF-β在骨肉瘤进展中的作用了解甚少。在本研究中，我们发现TGF-β在骨肉瘤细胞和组织中高表达，并且与高Ennecking阶段相关（P= 0.033），转移和复发。使用siRNA（si-TGF-β）建立TGF-β-knockdown骨肉瘤细胞系。si-TGF-β转染的细胞表现出明显降低的增殖，迁移/侵袭和集落形成能力，并增加了细胞凋亡水平。此外，si-TGF-β处理可减少骨肉瘤细胞中的球状体大小，CD133阳性细胞的比例以及SOX-2，Nanog和Oct-3 / 4的表达。从机理上讲，PI3K / mTOR磷酸化受到TGF-β敲低的抑制。用25 µM LY294002（一种PI3K特异性抑制剂）进行预处理，可以进一步增强si-TGF-β诱导的骨肉瘤进展抑制作用。在一起