MFTZ-1,a novel topoisomerase Ⅱ poison,reduces constitutive and inducible HIF-1α accumulation and VEGF secretion independent of its Top2 inhibition
文献类型：会议论文
| 作者 | Dai M(代梅); Mou ZH(缪泽鸿)2 ; Ren X(任萱); Tong LJ(童林江)2; Yang N(杨娜); Li T(李婷); Lin LP(林莉萍)1; Shen YM(沈岳茅); Ding J(丁健)2
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| 出版日期 | 2009-04-09 |
| 页码 | 1 |
| 英文摘要 | Purpose:The macrolide compound MFTZ-1 has been identified as a novel topoisomeraseⅡ(Top2) inhibitor with potent in vitro and in vivo anti-tumor activities.This study was to further examine its effects on hypoxia-inducible factor-1α(HIF-1α) accumulation,vascular endothelial growth factor(VEGF) secretion and the possible mechanisms.Experimental Design: Western blotting,reverse transcription-PCR,real time-PCR,ELISA and small interference RNA (siRNA) analyses were used to investigate the impact of MFTZ-1 on HIF-1αaccumulation and on VEGF secretion and the possible mechanism.Angiogenesis inhibition was assessed by the human umbilical vascular cell(HUVEC) migration and tube formation.Results:MFTZ-1 reduced HIF-1αaccumulation driven by hypoxia or growth factors in human cancer cells.However, MFTZ-1 did not affect protein degradation or mRNA level of HIF-1α.By contrast,MFTZ-1 apparently inhibited both phosphatidylinositol-3-kinase(PI3K-Akt) and p42/p44 mitogen-activated protein kinase(MAPK) pathways.Further studies revealed that MFTZ-1 abrogated the HIF-1α-driven increase of VEGF mRNA and secretion.MFTZ-1 also lowered the basal level in VEGF secretion.The results reveal an important feature that MFTZ-1 can reduce VEGF secretion in a HIF-1α-dependent and HIF-1α-independent way.Moreover,MFTZ-1 disrupted tube formation of HUVEC stimulated by hypoxia or serum,and inhibited HUVEC migration and microvessel outgrowth from rat aortic ring.Furthermore,we showed that MFTZ-1 affected HIF-1αaccumulation and HUVECs tube formation independent of its Top2 inhibition. Conclusion:Our data collectively reveal that MFTZ-1 reduces constitutive and inducible HIF-1αaccumulation and VEGF secretion via PI3K-Akt and MAPK pathways,eliciting antiangiogenesis independently of its Top2 inhibition. |
| 会议录 | 2009医学前沿论坛暨第十一届全国肿瘤药理与化疗学术会议论文集
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| 文献子类 | Article |
| 语种 | 英语 |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/267394]  |
| 专题 | 药理学第一研究室 科研与新药推进处 国家新药筛选中心 |
| 作者单位 | 1.中国科学院上海药物研究所,科研与新药推进处,上海 201203, 中国. 2.中国科学院上海药物研究所,药理学第一研究室,上海 201203, 中国.; |
| 推荐引用方式 GB/T 7714 | Dai M,Mou ZH,Ren X,et al. MFTZ-1,a novel topoisomerase Ⅱ poison,reduces constitutive and inducible HIF-1α accumulation and VEGF secretion independent of its Top2 inhibition[C]. 见:. |
入库方式： OAI收割
来源：上海药物研究所
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