Wang Ting, Xu Peipei, Wang Fan, Zhou Di, Wang Ruju, Meng Li, Wang Xiaohui, Zhou Min, Chen Bing, Ouyang Jian
a Department of Hematology , Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School , Nanjing , PR China.
b Department of Hematology , Nanjing Drum Tower Hospital, Clinical College of Medical College of Southeast University , Nanjing , PR China.
Leuk Lymphoma. 2017 Jul;58(7):1673-1685. doi: 10.1080/10428194.2016.1256480. Epub 2017 Jan 13.
Digoxin has potential antitumor properties. This study investigated whether digoxin suppressed Burkitt's lymphoma (BL) cells. Raji and NAMALWA cells were exposed to digoxin, followed by assay of cell viability, apoptosis and cell cycle. Western blotting was used to analyze NF-κB activity. A xenograft model was established for therapeutic efficacy evaluation. Digoxin inhibited cell growth and resulted in apoptosis and cell cycle arrest (G0/G1 for Raji cells; G2/M for NAMALWA cells). Digoxin inhibited DNA synthesis and induced morphological apoptotic characteristics. Besides, digoxin inhibited NF-κB and TNF-α-stimulated NF-κB activity, and suppressed NF-κB initiating genes (Bcl-2, Bcl-xL, cyclin D1, and c-myc), however, increased p21. Digoxin activated caspase-9/3. Furthermore, digoxin inhibited xenograft tumors growth and reduced Ki-67 and c-myc. Digoxin exerted antitumor effects on BL cells in vitro and in vivo might through regulating NF-κB and caspase pathway. These outcomes highlight the potential of digoxin as a therapeutic agent for BL.
地高辛具有潜在的抗肿瘤特性。本研究调查了地高辛是否能抑制伯基特淋巴瘤（BL）细胞。将拉吉细胞和纳马尔瓦细胞暴露于地高辛，随后检测细胞活力、凋亡和细胞周期。采用蛋白质免疫印迹法分析核因子κB（NF-κB）活性。建立异种移植模型用于评估治疗效果。地高辛抑制细胞生长，导致细胞凋亡和细胞周期阻滞（拉吉细胞为G0/G1期；纳马尔瓦细胞为G2/M期）。地高辛抑制DNA合成并诱导形态学上的凋亡特征。此外，地高辛抑制NF-κB以及肿瘤坏死因子-α（TNF-α）刺激的NF-κB活性，并抑制NF-κB启动基因（Bcl-2、Bcl-xL、细胞周期蛋白D1和c-myc），然而，p21增加。地高辛激活半胱天冬酶-9/3。此外，地高辛抑制异种移植肿瘤的生长，并降低Ki-67和c-myc。地高辛可能通过调节NF-κB和半胱天冬酶途径在体外和体内对BL细胞发挥抗肿瘤作用。这些结果凸显了地高辛作为BL治疗药物的潜力。
