Department of Hematology, Third Hospital of Hebei Medical University, Shijiazhuang, China.
Leuk Lymphoma. 2013 Mar;54(3):607-18. doi: 10.3109/10428194.2012.720371. Epub 2012 Sep 3.
Norcantharidin (NCTD), the demethylated analog of the Chinese medicine cantharidin, exhibits anti-myeloma activity by inactivating nuclear factor-κB (NF-κB), which is implicated in multiple myeloma (MM) cell survival and resistance to bortezomib (BTZ). We investigated whether NCTD could potentiate the anti-tumor activity of BTZ in MM. NCTD inhibited the proliferation of MM cells and potentiated the anti-myeloma effects of BTZ by down-regulating IKKα and p-IκBα, which induced the accumulation of IκBα and inhibited the constitutive activation of NF-κB. This effect was correlated with the suppression of NF-κB-regulated gene products. Furthermore, a chemotherapy-potentiating effect of NCTD on BTZ was also observed in vivo. Our study demonstrated that NCTD and BTZ exhibit significant therapeutic effects on MM through the NF-κB signal pathway in vitro and in vivo. Future studies will investigate the combined effects of NCTD and BTZ in patients with MM.
去甲基斑蝥素（NCTD）是中药斑蝥素的去甲基类似物，通过使核因子-κB（NF-κB）失活，发挥抗骨髓瘤作用，NF-κB 参与多发性骨髓瘤（MM）细胞的存活和对硼替佐米（BTZ）的耐药性。我们研究了 NCTD 是否可以增强 BTZ 在 MM 中的抗肿瘤活性。NCTD 通过下调 IKKα 和 p-IκBα 抑制 MM 细胞的增殖并增强 BTZ 的抗骨髓瘤作用，这导致 IκBα 的积累并抑制 NF-κB 的组成性激活。这种作用与抑制 NF-κB 调节的基因产物有关。此外，还观察到 NCTD 在体内对 BTZ 的化疗增强作用。我们的研究表明，NCTD 和 BTZ 通过体外和体内的 NF-κB 信号通路对 MM 具有显著的治疗作用。未来的研究将研究 NCTD 和 BTZ 联合应用于 MM 患者的效果。
