摘要

肿瘤坏死因子相关凋亡诱导配体（TRAIL）是一种很有前途的抗骨髓瘤药物原型。本研究旨在探讨环丙胺和循环置换TRAIL（CPT）对多发性骨髓瘤细胞增殖和凋亡的协同作用。结果表明，环丙胺对人骨髓瘤RPMI‑8226和SKO‑007细胞增殖的抑制作用较弱。RPMI‑8226细胞对CPT敏感，但对SKO‑007细胞的增殖没有有效的抑制作用。因此，SKO‑007细胞被认为对环胺和CPT具有耐药性，并用于随后的实验。环丙胺和CPT联合应用可显著抑制细胞增殖。此外，Q值显示环丙胺与CPT联用可协同抑制SKO‑007细胞的增殖。环丙胺增加了CPT诱导的SKO‑007细胞凋亡，并与CPT合用时表现出协同诱导凋亡作用。此外，环丙胺和CPT联合应用可降低骨髓瘤干细胞的比例。定量PCR结果显示，环丙胺可降低GLI1/GLI2/GLI3的mRNA表达水平，增加死亡受体4的表达水平。综上所述，本研究表明环丙胺和CPT联合应用对骨髓瘤细胞的增殖抑制和凋亡诱导具有协同作用。

Tumor necrosis factor related apoptosis inducing ligand (TRAIL) is a promising anti‑myeloma drug prototype. The aim of the present study was to investigate the synergistic effects of cyclopamine and circularly permuted TRAIL (CPT) on the proliferation and apoptosis of multiple myeloma cells. The results showed that the inhibitory effects of cyclopamine on the proliferation of human myeloma RPMI‑8226 and SKO‑007 cells were weak. RPMI‑8226 cells were sensitive to CPT; however, the proliferation of SKO‑007 cells was not effectively inhibited by CPT. SKO‑007 cells were thus considered resistant to cyclopamine and CPT and used for subsequent experiments. Treatment with a combination of cyclopamine and CPT significantly inhibited cell proliferation. Moreover, the Q value showed that cyclopamine combined with CPT could synergistically inhibit the proliferation of SKO‑007 cells. Cyclopamine increased CPT‑induced apoptosis in the SKO‑007 cells and exhibited a synergistic induction of apoptosis when combined with CPT. Moreover, the combination of cyclopamine and CPT decreased the ratio of myeloma stem cells. Quantitative PCR showed that cyclopamine decreased the mRNA expression levels of GLI1/GLI2/GLI3 and increased the expression levels of death receptor 4. In conclusion, the present study showed that a combination of cyclopamine and CPT exhibited synergistic effects on the inhibition of proliferation and induction of apoptosis in myeloma cells.