Anti-tumor effects of triptolide on angiogenesis and cell apoptosis in osteosarcoma cells by inducing autophagy via repressing Wnt/β-Catenin signaling

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.