Chen Ping, Yuan Qin, Yang Hui, Wen Xiaofang, You Peidong, Hou Diyu, Xie Jieqiong, Cheng Yu, Huang Huifang
Fujian Institute of Hematology, Fujian Provincial Key Laboratory of Hematology, Fujian Medical University Union Hospital,29 Xinquan Road, Fuzhou, Fujian, PR China.
The Central Laboratory, Fujian Medical University Union Hospital,29 Xinquan Road, Fuzhou, Fujian, PR China.
Leuk Res. 2017 Jun;57:119-126. doi: 10.1016/j.leukres.2017.04.007. Epub 2017 Apr 25.
Despite the great progress in the treatment, multiple myeloma (MM) still remains incurable. Bortezomib (BTZ), a reversible inhibitor of the 26S proteasome, is very effective against MM but unable to eradicate the MM cells in bone marrow niche eventually causing the disease relapse. Homoharringtonine (HHT) is a known anti-leukemia drug that inhibits MM both in vitro and in vivo. This study aimed to investigate whether HHT could potentiate the anti-tumor activity of BTZ in MM cells cocultured with bone marrow stromal cells and in vivo xenograft models. We found that coculture of myeloma cells with a human stroma cell line significantly decreased the sensitivity of myeloma cells to BTZ treatment. HHT inhibited the proliferation of MM cells and potentiated the anti-myeloma effects of BTZ by inhibition of both canonical and noncanonical NF-κB pathways. HHT also enhanced the anti-myeloma effect of BTZ in vivo xenograft models. Taken together, our data suggest that HHT can enhance the anti-myeloma activity of BTZ both in vitro and in vivo, which may represent a new clinical treatment in MM.
尽管在治疗方面取得了巨大进展，但多发性骨髓瘤（MM）仍然无法治愈。硼替佐米（BTZ）是一种26S蛋白酶体的可逆抑制剂，对MM非常有效，但最终无法根除骨髓微环境中的MM细胞，从而导致疾病复发。高三尖杉酯碱（HHT）是一种已知的抗白血病药物，在体外和体内均能抑制MM。本研究旨在探讨HHT是否能增强硼替佐米在与骨髓基质细胞共培养的MM细胞以及体内异种移植模型中的抗肿瘤活性。我们发现骨髓瘤细胞与人基质细胞系共培养显著降低了骨髓瘤细胞对硼替佐米治疗的敏感性。HHT通过抑制经典和非经典NF-κB途径抑制MM细胞增殖并增强硼替佐米的抗骨髓瘤作用。HHT在体内异种移植模型中也增强了硼替佐米的抗骨髓瘤作用。综上所述，我们的数据表明，HHT在体外和体内均可增强硼替佐米的抗骨髓瘤活性，这可能代表MM的一种新的临床治疗方法。
