Department of Hematology, Tianjin Medical University General Hospital, Tianjin, China.
J Investig Med. 2019 Jan;67(1):39-47. doi: 10.1136/jim-2018-000780. Epub 2018 Jul 11.
Multiple myeloma (MM) is characterized by the proliferation of malignant plasma cells and a subsequent overabundance of monoclonal paraproteins (M proteins). Everolimus works similarly to sirolimus as a mammalian target of rapamycin (mTOR) inhibitor. Bortezomib was the first therapeutic proteasome inhibitor to be tested in humans with MM. However, the combination of these two drugs for the treatment of MM has been rarely reported. In this study, we compared the therapeutic effects of everolimus and bortezomib, as well as those of a combination of everolimus and bortezomib, using an in vitro MM cell line model and in vivo xenograft mouse model. Our results showed that the synergistic antitumor effects of everolimus and bortezomib have significant inhibitory effect through inhibition of the AKT/mTOR pathway in both the MM cell lines and MM-bearing mice model. Our results provided evidence that the mTOR inhibitor, everolimus, will be a potential drug in MM therapy.
多发性骨髓瘤（MM）的特征是恶性浆细胞的增殖和随后单克隆免疫球蛋白（M 蛋白）的过量。依维莫司作为哺乳动物雷帕霉素靶蛋白（mTOR）抑制剂，其作用类似于西罗莫司。硼替佐米是第一种在 MM 患者中进行试验的治疗性蛋白酶体抑制剂。然而，这两种药物联合治疗 MM 的报道很少。在这项研究中，我们使用体外 MM 细胞系模型和体内异种移植小鼠模型，比较了依维莫司和硼替佐米以及依维莫司和硼替佐米联合应用的治疗效果。我们的结果表明，依维莫司和硼替佐米的协同抗肿瘤作用通过抑制 AKT/mTOR 通路，对 MM 细胞系和 MM 荷瘤小鼠模型均具有显著的抑制作用。我们的研究结果为 mTOR 抑制剂依维莫司在 MM 治疗中的应用提供了证据。
