Opposite angiogenic outcome of curcumin against ischemia and Lewis lung cancer models:in silico,in vitro and in vivo studies
The aim of this study was to investigate the angiogenic effects of curcumin on an ischemia and lung cancer model.To induce ischemia combined with lung cancer models,unilateral femoral arteries of C57BL/6 mice were disconnected on one side of the mouse and Lewis lung carcinoma(LLC)cells were xenografted on the opposite side.Angiogenic effects and underlying mechanisms associated with curcumin were investigated.Molecular larget(s),signaling cascades and binding affinities were delected by Western blot,two-dimensional gel electrophoresis(2-DE),computer simulations and surface plasmon resonance(SPR)techniques.Curcumin promoted post-ischemic blood recirculation and suppressed lung cancer progression in inbred C57BL/6 mice via regulation of the HIF1α/mTQR/VECF/VEGFR cascade oppositely.Inflammatory stimulation induced by neutrophil elaslase(NE)promoted angiogenesis in lung cancer tissues,but these changes were reversed by curuimin through directly reducing NE secretion and stimulating α1-antitrypsin(α1-AT)and insulin receptor substrate-1(IRS-1)production.Meanwhile,curcumin dosc-dependently influenced endothelial cells(EC)tube formation and thicken embryo chorioallantoic membiane(CAM)neovasctilarization.Curcumin had opposite effects on blood vessel regeneration under physiological and pathological angiogenesis,which was effected through negative or positive regulation of the HIF1α/mTOR/VEGF/VEGFR cascade.Curcumin had the promise as a new treatment modality for both ischemic conditions and lung cancer simultaneously in the clinic.
Curcumin Angiogenesis Ischemia and lung cancer model Neutrophil elastase
Shengjun Fan Yan Xu Xin Li Lu Tie Yan Pan Xuejun Li
State Key Laboratory of Natural and Biomimetic Drugs,Department of Pharmacology,School of Bask Medical Sciences,Peking University Health Science Center,Beijing Key Laboratory of Tumor Systems Biology,Peking University,Beijing 100191,China
国内会议
大连
英文
657-669
2016-09-24（万方平台首次上网日期，不代表论文的发表时间）