Liang Yun, He Xin, Li Xian, Zhang Xuzhao, Zhang Xiaohong, Zhang Lei, Qiu Xi, Zhao Xiaoying, Xu Rongzhen
a Department of Hematology , The Second Affiliated Hospital of Zhejiang University of Medicine , Hangzhou , Zhejiang , China.
Cancer Invest. 2016 Nov 25;34(10):496-505. doi: 10.1080/07357907.2016.1235709. Epub 2016 Oct 21.
Multiple myeloma (MM) remains incurable despite the development and the use of new agents. In our studies, we found that 4-chlorbenzoyl berbamine (BBMD9), a novel synthetic derivative of berbamine, inhibited the proliferation of MM cells in dose- and time-dependent manners. Flow cytometric (FCM) analysis revealed that MM cells were arrested in the G1 phase and that apoptotic cells increased in a time-dependent manner. Moreover, the BBMD9 treatment downregulated IKKα and IKKβ, inhibited p-IκBα, and blocked p65 nuclear localization. Consistently, NF-κB downstream targets, such as cyclinD1 and survivin, were also reduced. In addition, BBMD9 phosphorylated the activity of JNK and c-Jun.
尽管有新型药物的研发和应用，多发性骨髓瘤（MM）仍然无法治愈。在我们的研究中，我们发现小檗胺的新型合成衍生物4-氯苯甲酰小檗胺（BBMD9）以剂量和时间依赖性方式抑制MM细胞的增殖。流式细胞术（FCM）分析显示，MM细胞停滞于G1期，且凋亡细胞呈时间依赖性增加。此外，BBMD9处理下调了IKKα和IKKβ，抑制了p-IκBα，并阻止了p65的核定位。同样，NF-κB下游靶点，如细胞周期蛋白D1和生存素，也减少了。此外，BBMD9使JNK和c-Jun的活性磷酸化。
