Department of Histology and Embryology, Basic Medical College, Hebei United University, Tangshan, China.
Anticancer Drugs. 2013 Jul;24(6):609-16. doi: 10.1097/CAD.0b013e3283615006.
The proteasome inhibitor bortezomib has been applied successfully to treat multiple myeloma (MM). Its synergistic effects with other anticancer drugs have been studied widely. In the present study, it was found that lidamycin (LDM), a member of the enediyne antibiotic family, showed much more potent cytotoxicity than bortezomib to MM cell lines: U266 and SKO-007. Here, we investigated the potential synergy of bortezomib and LDM on MM cells. The results showed that cotreatment of bortezomib and LDM synergistically induced cytotoxicity and apoptosis in MM cell lines, followed by enhanced caspase-3 cleavage and degradation of poly-ADP-ribose polymerase together with the decreased nuclear factor-κB protein. These two drugs synergistically induced apoptosis, which was associated with enhanced activation of two mitogen-activated protein kinases: p38 mitogen-activated protein kinase and c-Jun NH(2)-terminal kinase. Moreover, bortezomib plus LDM synergistically induced apoptosis was also associated with downregulation of extracellular signal-regulated kinase, and induction of endoplasmic reticulum stress response. Overall, our results indicate that the combined regimen of bortezomib and LDM might be a potential therapeutic remedy for the treatment of MM.
蛋白酶体抑制剂硼替佐米已成功应用于多发性骨髓瘤（MM）的治疗。其与其他抗癌药物的协同作用已被广泛研究。在本研究中，发现烯二炔抗生素家族的成员榄香烯（LDM）对 MM 细胞系 U266 和 SKO-007 的细胞毒性比硼替佐米强得多。在这里，我们研究了硼替佐米和 LDM 对 MM 细胞的潜在协同作用。结果表明，硼替佐米和 LDM 联合处理可协同诱导 MM 细胞系的细胞毒性和细胞凋亡，随后 caspase-3 裂解和聚 ADP-核糖聚合酶降解增强，核因子-κB 蛋白减少。这两种药物协同诱导的凋亡与两种丝裂原激活的蛋白激酶（p38 丝裂原激活的蛋白激酶和 c-Jun NH2-末端激酶）的激活增强有关。此外，硼替佐米加 LDM 协同诱导的凋亡也与细胞外信号调节激酶的下调和内质网应激反应的诱导有关。总之，我们的研究结果表明，硼替佐米和 LDM 的联合治疗方案可能是治疗 MM 的一种潜在治疗方法。
