Wu Yong-Tao, Wang Bao-Jun, Miao Sheng-Wu, Gao Jian-Jun
Department of Pediatric Orthopedics, Hong Hui Hospital, Xi'an Jiaotong University College Medicine, Xi'an, Shaanxi 710054, P.R. China.
Department of Orthopedics, Shaanxi Province Yangling Demonstration Zone Hospital, Yangling, Shaanxi 712100, P.R. China.
Mol Med Rep. 2015 Nov;12(5):7045-50. doi: 10.3892/mmr.2015.4266. Epub 2015 Aug 28.
Ewing's sarcoma (ES) is the second most common type of pediatric bone tumor, and is associated with a poor prognosis. Picropodophyllin (PPP), a novel selective inhibitor of insulin‑like growth factor‑1 receptor (IGF‑1R), is able to strongly inhibit various types of cancers. However, the effect of IGF‑1R on ES remains unclear. Following treatment with various concentrations of PPP for various times, cell viability was determined using an MTT assay. In addition, cell proliferation and apoptosis was investigated separately by bromodeoxyuridine staining and flow cytometry, respectively. The PPP‑associated signaling pathway was also investigated. The results of the present study suggested that PPP inhibited cell proliferation and viability of A673 and SK‑ES‑1 human Ewing's sarcoma cells in a dose- and time‑dependent manner. In addition, cell apoptosis rates were increased following treatment with PPP. Further investigation of the underlying mechanism revealed that PPP inhibited Akt phosphorylation. Fumonisin B1, an Akt‑specific activator, reversed the inhibitory effects of PPP on cell growth. Furthermore, the results suggested that PPP decreased the expression levels of IGF‑1R, a common activator of Akt signaling. PPP inhibited the growth of human Ewing's sarcoma cells by targeting the IGF‑1R/Akt signaling pathway. Therefore, PPP may prove useful in the development of an effective strategy for the treatment of Ewing's sarcoma.
尤因肉瘤（ES）是儿童期第二常见的骨肿瘤类型，且预后较差。鬼臼苦素（PPP）是一种新型的胰岛素样生长因子-1受体（IGF-1R）选择性抑制剂，能够强烈抑制多种类型的癌症。然而，IGF-1R对ES的影响仍不清楚。用不同浓度的PPP处理不同时间后，采用MTT法测定细胞活力。此外，分别通过溴脱氧尿苷染色和流式细胞术研究细胞增殖和凋亡。还研究了与PPP相关的信号通路。本研究结果表明，PPP以剂量和时间依赖性方式抑制A673和SK-ES-1人尤因肉瘤细胞的增殖和活力。此外，用PPP处理后细胞凋亡率增加。对潜在机制的进一步研究表明，PPP抑制Akt磷酸化。伏马菌素B1是一种Akt特异性激活剂，可逆转PPP对细胞生长的抑制作用。此外，结果表明PPP降低了Akt信号常见激活剂IGF-1R的表达水平。PPP通过靶向IGF-1R/Akt信号通路抑制人尤因肉瘤细胞的生长。因此，PPP可能在开发治疗尤因肉瘤的有效策略中发挥作用。
