Inhibition of survivin expression suppresses the growth of aggressive non-Hodgkin's lymphoma
Inhibition of survivin expression suppresses the growth of aggressive non-Hodgkin's lymphoma
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DOI：
10.1038/sj.leu.2403281
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发表时间：
2004-03-01
期刊：
影响因子：
11.4
通讯作者：
Fielding, A
中科院分区：
文献类型：
--
作者：
Ansell, SM;Arendt, BK;Fielding, A
生存素是细胞凋亡抑制蛋白（IAP）家族的成员，既是细胞凋亡抑制剂，又是细胞分裂调节剂。生存素过表达在许多人类肿瘤中很常见，并且与大细胞非霍奇金淋巴瘤的生存相关。为了评估这种分子作为大细胞淋巴瘤的潜在治疗靶点，我们在体外和体内评估了生存素抑制的效果。使用反义寡核苷酸（阿索）的方法，细胞生长显着抑制DoHH 2，RL和HT淋巴瘤细胞系。在淋巴瘤异种移植模型中，与对照相比，存活素ASO处理的小鼠中肿瘤的发展以及已建立的肿瘤的生长受到抑制。为了评估生存素阿索与其他生物制剂组合的功效，我们将生存素阿索与抗CD20单克隆抗体利妥昔单抗组合。Survivin阿索和利妥昔单抗的联合作用在体外是相加的。然而，在体内，联合用药对肿瘤生长的抑制并不明显优于对照组的上级效果。我们的结论是，抑制生存素的表达是一个有吸引力的治疗策略，在侵略性非霍奇金淋巴瘤，并结合生存素阿索与利妥昔单抗可能会提高这种方法的疗效。
Survivin is a member of the inhibitor of apoptosis protein (IAP) family and functions both as an apoptosis inhibitor and a regulator of cell division. Survivin overexpression is common in many human tumors and correlates with survival in large cell non-Hodgkin's lymphoma. To evaluate this molecule as a potential therapeutic target in large-cell lymphoma, we evaluated the effect of survivin inhibition both in vitro and in vivo. Using an antisense oligonucleotide (ASO) approach, cell growth was significantly inhibited in the DoHH2, RL and HT lymphoma cell lines. In a lymphoma xenograft model, the development of tumors as well as the growth of established tumors was inhibited in the survivin ASO-treated mice compared to controls. To assess the efficacy of the survivin ASO in combination with other biological agents, we combined the survivin ASO with an anti-CD20 monoclonal antibody, rituximab. The effect of survivin ASO and rituximab in combination was additive in vitro. In vivo, however, suppression of tumor growth with the combination was not significantly superior to controls. We conclude that inhibition of survivin expression is an attractive therapeutic strategy in aggressive non-Hodgkin's lymphomas, and that combining survivin ASO with rituximab may enhance the efficacy of this approach.