AMD3100 combined with triptolide inhibit proliferation, invasion and metastasis and induce apoptosis of human U2OS osteosarcoma cells

作者：Jiang, Chunming; Fang, Xiang; Zhang, Hongxu; Wang, Xuepeng; Li, Maoqiang; Jiang, Wu; Tian, Fei; Zhu, Liulong^*; Bian, Zhenyu^*

来源：Biomedicine & Pharmacotherapy, 2017, 86: 677-685.

DOI：10.1016/j.biopha.2016.12.055

• Osteosarcoma
• AMD3100
• Triptolide
• Erk1/2
• Akt
• STAT3

Background: Osteosarcoma (OS) mainly occurs in children and adolescents, and has a high propensity for lung metastasis. Little is known about the role of SDF-1/CXCR4 axis in OS progression. AMD3100 is a specific CXCR4 antagonist. Triptolide can induce apoptosis and proliferation inhibition in various cancer cell lines. @@@ Objective: This work aimed to investigate the effects of AMD3100 plus triptolide on the proliferation, apoptosis, invasion and metastasis of OS cells. @@@ Methods: The expression levels of SDF-1 and CXCR4 in five OS cell lines was analyzed by qRT-PCR, western blotting and ELISA assays. The effect of AMD3100 and triptolide on the proliferation, apoptosis and invasion of U2OS cells was evaluated by CCK-8, flow cytometry and transwell assay, respectively. Orthotopic intra-tibial growth and lung metastasis mouse model of OS were employed to evaluate the inhibition effect of AMD3100 and triptolide on primary OS growth and lung metastasis. @@@ Results: CXCR4 protein expression was detected in HOS-8603, MG-63, U2OS and 143B but not Saos2 cells, and all these cell lines expressed SDF-1. AMD3100 plus triptolide induced proliferation inhibition and apoptosis of U2OS cells, which was attributed to the downregulation of c-Myc, survivin, cyclin D1 and increased cleaved caspase-3 and PARP. AMD3100 and triptolide also suppressed SDF-1 induced invasion of CXCR4+ U2OS cells, which was validated by decreased expression of MMP-2 and 9, VEGF, m-Calpain and beta-catenin. Moreover, the phosphorylation levels of Erk1/2, Akt and STAT3, as well as the nuclear translocation and phosphorylation of NF-kappa B p65 in U2OS cells were also reduced by AMD3100 and triptolide. In vivo, AMD3100 and triptolide significantly reduced primary tumor growth and lung metastasis of U2OS cells. @@@ Conclusions: AMD3100 combined with triptolide can reduce proliferation and metastasis, and induce apoptosis of U2OS cells, which may be related to the Erk1/2, Akt, STAT3 and NF-kappa B pathways.

• 出版日期2017-2
• 单位南京医科大学