沙利度胺可下调活动性多发性骨髓瘤患者骨髓内皮细胞中的血管生成基因。

Thalidomide downregulates angiogenic genes in bone marrow endothelial cells of patients with active multiple myeloma.

作者信息

Vacca Angelo, Scavelli Claudio, Montefusco Vittorio, Di Pietro Giulia, Neri Antonino, Mattioli Michela, Bicciato Silvio, Nico Beatrice, Ribatti Domenico, Dammacco Franco, Corradini Paolo

机构信息

Department of Internal Medicine and Clinical Oncology, Policlinico-Piazza Giulio Cesare, University of Medical School Bari, Italy.

出版信息

J Clin Oncol. 2005 Aug 10;23(23):5334-46. doi: 10.1200/JCO.2005.03.723. Epub 2005 Jun 6.

DOI:10.1200/JCO.2005.03.723

PMID:15939924

Abstract

PURPOSE

To study the antiangiogenic effect of thalidomide.

PATIENTS AND METHODS

The expression of key angiogenic genes was studied in bone marrow endothelial cells (ECs) of patients with active and nonactive multiple myeloma (MM), monoclonal gammopathies unattributed/unassociated (MG[u]), diffuse large B-cell non-Hodgkin's lymphoma, in a Kaposi's sarcoma (KS) cell line, and in healthy human umbilical vein ECs (HUVECs) following exposure to therapeutic doses of thalidomide.

RESULTS

Thalidomide markedly downregulates the genes in a dose-dependent fashion in active MMECs and KS cell line, but upregulates them or is ineffective in nonactive MMECs, MG(u)ECs, NHL-ECs, and in HUVECs. Secretion of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) and hepatocyte growth factor also diminishes according to the dose in culture conditioned media (CM) of active MMECs and KS, whereas it does not change in the other CM.

CONCLUSION

Inhibition by thalidomide is probably confined to the genes of active MMECs and KS. This would account for its higher efficacy in these diseases.

摘要

目的

研究沙利度胺的抗血管生成作用。

患者与方法

在活动性和非活动性多发性骨髓瘤（MM）、未分类/未关联的单克隆丙种球蛋白病（MG[u]）、弥漫性大B细胞非霍奇金淋巴瘤患者的骨髓内皮细胞（ECs）中，在卡波西肉瘤（KS）细胞系中，以及在接受治疗剂量沙利度胺处理后的健康人脐静脉内皮细胞（HUVECs）中，研究关键血管生成基因的表达。

结果

沙利度胺在活动性MMECs和KS细胞系中以剂量依赖方式显著下调基因，但在非活动性MMECs、MG[u]ECs、NHL-ECs以及HUVECs中上调这些基因或无作用。在活动性MMECs和KS的培养条件培养基（CM）中，血管内皮生长因子（VEGF）、碱性成纤维细胞生长因子（bFGF）和肝细胞生长因子的分泌也随剂量减少，而在其他CM中则无变化。