Lidamycin inhibits proliferation and induces apoptosis in endot helial cells  

作　　者：王心华[1] 吴淑英[1] 甄永苏[1] 

机构地区：[1]中国医学科学院中国协和医科大学医药生物技术研究所,北京100050

出　　处：《中国抗生素杂志》2003年第10期605-612,共8页Chinese Journal of Antibiotics

基　　金：This study was supported by a grant from China State Key Basic Research Project(G1998051212);a grant from National Foundation for Cancer Research,USA.

摘　　要：目的　研究力达霉素 (lidamycin,L DM)对内皮细胞的增殖抑制作用和诱导细胞凋亡作用。方法　用 MTT测定法和[3H]胸苷掺入测定法观察 L DM对内皮细胞的增殖抑制 ;用流式细胞分析、形态观察、蛋白质印迹分析等方法研究 L DM诱导内皮细胞凋亡及对相关调节蛋白的影响。结果　L DM呈浓度依赖性抑制内皮细胞增殖和诱导内皮细胞凋亡。L DM浓度 1～ 10 nmol/L可将内皮细胞阻断在 G2 /M期。L DM可导致内皮细胞中的游离钙增高 ,可使 Bc1-2和 PCNA蛋白的表达下调 ,但对 Bax蛋白的表达无影响。结论　力达霉素抑制内皮细胞增殖与诱导内皮细胞凋亡 。Lidamycin (LDM), a new macromolecular anti bi otic with an enediyne chromophore, also called C1027, displays extremely potent cytotoxicity against cancer cells. Our previous study showed LDM inhibited angio genesis and tumor growth and metastasis. In present study, the effect of LDM on the proliferation and the apoptosis of endothelial cells as well as the change o f endothelial cells intracellular free calcium were observed. Growth inhibition was measured by MTT assay and thymidine incorporation assay. LDM inhibi ted the proliferation of endothelial cells with or without the stimulation of ba sic-fibroblast growth factor (bFGF) in a dose-dependent manner; 1～10 nmol/L L DM blocked the cell cycle in G 2/M phase after 12h treatment; 10～100 nmol/L LD M induced a dose-dependent apoptosis of endothelial cells under the same condit ion, as determined by morphological assessment, DNA laddering and flow cytometry analysis. Moreover, LDM caused a marked increase of intracellular free calcium in endothelial cells. Western blot analysis showed the down-regulation of Bcl- 2 and PCNA protein expression in endothelial cells, whereas Bax protein levels w ere unaffected. Collectively, these findings provide important mechanistic insig ht into the anti-angiogenic action of LDM.

关 键 词：力达霉素 血管生成 内皮细胞 细胞增殖 细胞凋亡 

分 类 号：Q933[生物学—微生物学]