姜黄素类似物BDDD-721靶向Shh/Gli1通路抗髓母细胞瘤作用研究

Abstract

Medulloblastoma (MB) is a malignant tumor in the fourth ventricle of children. The clinical treatment is mainly surgical resection combined with radiotherapy and chemotherapy, but the curative effect is not ideal, and the 3-year survival rate is very low. Previous study confirmed that curcumin attenuated the proliferation of medulloblastoma both in vitro and in vivo . In present study, we found a curcumin analogue named BDDD-721, exhibited more potent anti-tumor activity than curcumin. Compared with curcumin, BDDD-721 more effectively inhibited the proliferation, migration, invasion, and increased apoptosis of medulloblastoma cells. Furthermore, BDDD-721 treatment led to activation of glioma-associated oncogene homolog (Gli), reduced expression of Shh and its downstream target Smo, Gli1 and Ptch1. In addition, SAG (Shh signaling pathway agonist) antagonized the pro-apoptotic effects of BDDD-721 on medulloblastomas as confirmed by CCK8 assays and flow cytometry; while cyclopamine (Shh signaling pathway inhibitor) enhanced its effects on medulloblastomas. In conclusion, these results indicate that curcumin analogue BDDD-721 has more potent anticancer effects than curcumin on medulloblastomas by targeting Shh/Gli1 signaling pathway.