Romagnoli M, Trichet V, David C, Clément M, Moreau P, Bataille R, Barillé-Nion S
1INSERM, UMR 601, 9 quai Moncousu, Nantes, F-44093, France.
Leukemia. 2007 May;21(5):1070-8. doi: 10.1038/sj.leu.2404602. Epub 2007 Feb 22.
Survivin is a fascinating member of the inhibitor of apoptosis protein (IAP) family with its dual roles in mitosis and apoptosis, and emerges as an attractive target for cancer therapy. Multiple myeloma (MM) is a plasma cell malignancy, characterized by deregulated proliferation, cell-death processes and fatal outcome. We thus investigated survivin expression in myeloma cells and its role in MM biology to evaluate its potential interest as a target in MM treatment. Our results describe the cancer-specific overexpression of survivin in myeloma cells and show a significant correlation between survivin expression at protein level and clinical course of MM. Moreover, survivin knockdown by RNA interference led to growth rate inhibition of myeloma cells related to apoptosis induction and deep cell-cycle disruption. Finally, survivin knockdown sensitized myeloma cells to conventional anti-myeloma agents. Altogether, these data argue for the interest to evaluate survivin antagonists in MM treatment.
生存素是凋亡抑制蛋白(IAP)家族中一个引人关注的成员,它在有丝分裂和凋亡过程中具有双重作用,并成为癌症治疗中一个有吸引力的靶点。多发性骨髓瘤(MM)是一种浆细胞恶性肿瘤,其特征为增殖失调、细胞死亡过程异常以及致命的结局。因此,我们研究了生存素在骨髓瘤细胞中的表达及其在MM生物学中的作用,以评估其作为MM治疗靶点的潜在价值。我们的结果描述了骨髓瘤细胞中生存素的癌症特异性过表达,并显示蛋白水平的生存素表达与MM的临床病程之间存在显著相关性。此外,通过RNA干扰敲低生存素导致骨髓瘤细胞生长速率受到抑制,这与凋亡诱导和深度细胞周期紊乱有关。最后,敲低生存素使骨髓瘤细胞对传统抗骨髓瘤药物敏感。总之,这些数据表明评估生存素拮抗剂在MM治疗中的价值是有意义的。