Division of Basic and Translational Research, Department of Surgery, University of Minnesota, United States.
Cancer Lett. 2013 Jul 28;335(2):412-20. doi: 10.1016/j.canlet.2013.02.050. Epub 2013 Mar 14.
Osteosarcoma is the most common bone cancer in children and adolescents with a 5-year survival rate of about 70%. In this study, we have evaluated the preclinical therapeutic efficacy of the novel synthetic drug, Minnelide, a prodrug of triptolide on osteosarcoma. Triptolide was effective in significantly inducing apoptosis in all osteosarcoma cell lines tested but had no significant effect on the human osteoblast cells. Notably, Minnelide treatment significantly reduced tumor burden and lung metastasis in the orthotopic and lung colonization models. Triptolide/Minnelide effectively downregulated the levels of pro-survival proteins such as heat shock proteins, cMYC, survivin and targets the NF-κB pathway.
骨肉瘤是儿童和青少年中最常见的骨癌，5 年生存率约为 70%。在这项研究中，我们评估了新型合成药物 Minnelide（雷公藤内酯醇的前体药物）治疗骨肉瘤的临床前治疗效果。雷公藤内酯醇可有效显著诱导所有测试的骨肉瘤细胞系发生凋亡，但对人成骨细胞没有明显作用。值得注意的是，Minnelide 治疗可显著减少骨肉瘤的原位和肺定植模型中的肿瘤负担和肺转移。雷公藤内酯醇/ Minnelide 可有效下调热休克蛋白、cMYC、survivin 等生存蛋白的水平，并靶向 NF-κB 通路。
