Anti-tumor effects of triptolide on angiogenesis and cell apoptosis in osteosarcoma cells by inducing autophagy via repressing Wnt/β-Catenin signaling
Anti-tumor effects of triptolide on angiogenesis and cell apoptosis in osteosarcoma cells by inducing autophagy via repressing Wnt/β-Catenin signaling
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DOI：
10.1016/j.bbrc.2018.01.052
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发表时间：
2018-02-05
影响因子：
3.1
通讯作者：
Wang, Guanqing
中科院分区：
文献类型：
--
作者：
Li, Xugui;Lu, Qilin;Wang, Guanqing
骨肉瘤是一种常见于青少年和儿童的恶性骨肿瘤。骨肉瘤预后差，5年生存率低，部分原因是骨肉瘤转移率高。雷公藤内酯醇（TPL）是雷公藤的一种提取物，广泛用于癌症治疗。本研究旨在探讨TPL在骨肉瘤治疗中的作用及其调控机制。我们的研究表明，TPL通过抑制缺氧诱导因子-1 α（HIF-1 α）和血管内皮生长因子（VEGF）的表达抑制血管生成，并呈剂量依赖性。TPL可明显诱导细胞凋亡，且呈剂量依赖性。进一步的研究表明，随着TPL浓度的增加，TPL诱导了明显的细胞自噬。自噬抑制剂3-MA的协同作用可阻断TPL的抗血管生成和促凋亡作用。此外，我们发现TPL可使Wnt/beta-Catenin信号通路失活，而通路诱导剂Lid的加入可中和TPL诱导自噬、抗血管生成和促凋亡的作用。综上所述，我们认为TPL通过抑制Wnt/β-Catenin信号通路诱导自噬，从而抑制骨肉瘤细胞的血管生成并诱导细胞凋亡。(C)2018爱思唯尔公司All rights reserved.
Osteosarcoma is a common malignant bone tumor occurring in adolescents and children. The poor prognosis and low 5-year survival rate of osteosarcoma partly due to high metastasis of osteosarcoma. Triptolide (TPL), an extract from Tripterygium wilfordii, is widely used in cancer treatment. In our present study, we aimed to study the effect of TPL in osteosarcoma treatment and explore the associated regulation mechanism. Our study revealed that TPL inhibited angiogenesis by suppressing the expression of hypoxia inducible factor-1 alpha (HIF-1 alpha) and vascular endothelial growth factor (VEGF) in dose dependent manner. Besides, cell apoptosis was induced by TPL obviously in dose dependent manner. Further study demonstrated that TPL induced obvious cell autophagy with increased concentration. The cooperation of autophagy inhibitor 3-MA abolished the effect of TPL on anti-angiogenesis and apoptosis promoting. Moreover, we found that Wnt/beta-Catenin signaling was inactivated by TPL and the adding of pathway inducer Lid neutralized the effect of TPL on autophagy induction, anti-angiogenesis and apoptosis promoting. Taken together, we suggested that TPL inhibited angiogenesis and induced cell apoptosis in osteosarcoma cells by inducing autophagy via repressing Wnt/beta-Catenin signaling. (C) 2018 Elsevier Inc. All rights reserved.