摘要
Wnt信号被认为是多发性骨髓瘤(MM)致癌作用的一个重要角色。为了观察Wnt/β-catenin信号通路在多发性骨髓瘤特别是多发性骨髓瘤干细胞中的表达及Wnt/β-catenin信号通路抑制剂CAY10404对多发性骨髓瘤的治疗作用,对13个多发性骨髓瘤患者的骨髓样本和多发性骨髓瘤细胞株中的Wnt/β-catenin相关基因的表达情况进行分析和运用Western-blot方法分析β-catenin蛋白在多发性骨髓瘤不同细胞亚群中的表达及COX2抑制剂CAY10404对β-catenin蛋白表达的抑制,通过体内外试验观察CAY1040对多发性骨髓瘤不同细胞亚群的增殖抑制作用。结果显示Wnt/β-catenin信号通路在多发性骨髓瘤病人样本CD138-/CD19+干细胞亚群中比CD138+细胞亚群表达显著增高(P<0.05);体内外试验显示CAY10404明显抑制多发性骨髓瘤干细胞亚群的增殖(P<0.05)。该研究通过靶向干预Wnt/β-catenin信号通路,对治疗多发性骨髓瘤尤其是多发性骨髓瘤干细胞进行了探索。
Wnt/β-catenin signaling pathway is involved in multiple myeloma. In order to evaluate the function of Wnt/β-catenin sig- naling pathway in the multiple myeloma, 13 bone marrow samples from muhlple myeloma patients and myeloma cell lines were analysed by micro-array, real-time PCR. Western blot was used to test the expression of β-eatenin in these samples, especially in multiple myeloma stem cells. COX2 inhibitor, CAY10404 was used to evaluate the effect of inhibtion Wnt signaling on the myeloma progression both in vitro and in vivo. Results showed that Wnt/β-eatenin signaling highly expressed in myeloma cells especially in myeloma stem cells （P 〈 0.05 ） and CAY10404 significantly inhibited proliferation of myeloma cells and tumorgenesis in Nod-Scid mice（ P 〈 0.05 ）. These findings provide a rationale for Wnt/β-catenin signaling pathway-based therapy in multiple myeloma, espe- cially in multiple myeloma stem cells.
出处
《药物生物技术》
CAS
2013年第2期128-132,共5页
Pharmaceutical Biotechnology
