RhPDCD5 combined with dexamethasone increases antitumor activity in multiple myeloma partially via inhibiting the Wnt signalling pathway
RhPDCD5 combined with dexamethasone increases antitumor activity in multiple myeloma partially via inhibiting the Wnt signalling pathway
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DOI：
10.1111/1440-1681.12859
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发表时间：
2018-02
影响因子：
2.9
通讯作者：
Qian Cheng;Liping Liu;Yunfeng Fu;Yanan Zhang;Ye Yang;Jing Liu
中科院分区：
文献类型：
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作者：
Qian Cheng;Liping Liu;Yunfeng Fu;Yanan Zhang;Ye Yang;Jing Liu
多发性骨髓瘤（MM）是最常见的恶性血液病之一，其特征是恶性浆细胞的克隆性积聚。近年来MM治疗取得了重大进展，但MM仍然无法治愈。我们前期研究发现重组人程序性细胞死亡基因5（rhPDCD 5）能促进地塞米松（Dex）诱导的MM细胞凋亡。在这里，我们通过显示单独的rhPDCD 5不能诱导U266细胞（MM细胞系）的明显生长抑制来扩展发现。值得注意的是，与地塞米松（Dex）的组合，MM细胞的生长被显著抑制，并伴有细胞周期停滞在G 0/G1期。在机制研究中，我们发现，与单独使用Dex相比，rhPDCD 5 + Dex联合治疗可下调Wnt效应因子β-catenin、β-catenin（Ser 675）、TCF 4、survivin和c-Myc的mRNA和蛋白表达。此外，由LiCl诱导的WNT途径的激活也可以通过这种组合处理来抑制。综上所述，我们的研究表明，rhPDCD 5和Dex的组合可以抑制多发性骨髓瘤细胞的增殖，部分通过抑制WNT信号通路。
Multiple myeloma (MM) is one of the most common hematological malignancies and characterized by the clonal accumulation of malignant plasma cells. Significant progress has been made in MM treatment recently, while MM still remains incurable. Our previous studies showed that the recombined human programmed cell death 5 (rhPDCD5) can promote MM apoptosis induced by dexamethasone (Dex). Here, we expanded the findings by showing that the rhPDCD5 alone could not induce an obvious growth inhibition of U266 cells (a MM cell line). Of note, with the combination of dexamethasone (Dex), the growth of MM cells was significantly inhibited and accompanied with the cell cycle arrest in G0/G1. For mechanism study, we found that the combination treatment of rhPDCD5 plus Dex downregulated the mRNA and protein expressions of Wnt effectors including β‐catenin, β‐catenin (Ser675), TCF4, survivin and c‐Myc when compared to Dex only. Moreover, the activation of WNT pathway induced by LiCl can also be inhibited by this combination treatment. Taken together, our study demonstrated that the combination of rhPDCD5 and Dex can suppress the proliferation of multiple myeloma cells partially via inhibiting the WNT signalling pathway.