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首页> 外文期刊>RSC Advances >A marine sponge associated fungal metabolite monacolin X suppresses angiogenesis by down regulating VEGFR2 signaling
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A marine sponge associated fungal metabolite monacolin X suppresses angiogenesis by down regulating VEGFR2 signaling

机译：海洋海绵相关的真菌代谢物莫纳可林X通过下调VEGFR2信号传导抑制血管生成

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摘要

Cancer is one of the leading causes of global death and there is an urgent need for the development of cancer treatment; targeting VEGFR2 could be one of the promising therapies. In the present study, previously isolated marine fungal metabolite monacolin X, suppresses in vitro angiogenic characteristics such as proliferation, migration, adhesion, invasion and tube formation of HUVECs when stimulated by VEGF, at a non-toxic concentration. Monacolin X downregulated VEGFR2, PKCα and PKCη mRNA expression. Further, monacolin X inhibited in vivo angiogenesis in CAM assay, vascular sprouting in aortic ring, decreased ISV and SIV length and diameter in Tg (Kdr:EGFP)/ko1 zebrafish embryos. Monacolin X showed reduced protein expression of pVEGFR2, pAKT1, pMAPKAPK2, pFAK and pERK1 in breast cancer lines and in DMBA induced mammary carcinoma in SD rats showed tumor regression and anti-angiogenesis ability via decrease pVEGFR2 and pAKT1 protein expression. In silico studies also revealed monacolin X ability to bind to crucial amino acid Cys 919 in the active site of VEGFR2 suggesting it to be a potent VEGFR2 inhibitor.
机译：癌症是全球性死亡的主要原因之一，迫切需要发展癌症治疗方法。靶向VEGFR2可能是有前途的治疗方法之一。在本研究中，先前分离的海洋真菌代谢物莫纳可林X在无毒浓度下被VEGF刺激时，可抑制HUVEC的体外血管生成特性，例如增殖，迁移，粘附，侵袭和管形成。莫纳可林X下调VEGFR2，PKCα和PKCηmRNA表达。此外，莫纳可林X在CAM分析中抑制体内血管生成，在主动脉环中发芽，降低Tg（Kdr：EGFP）/ ko1斑马鱼胚胎中ISV和SIV的长度和直径。莫纳可林X在乳腺癌细胞系中显示pVEGFR2，pAKT1，pMAPKAPK2，pFAK和pERK1的蛋白表达降低，而在DMBA诱导的SD大鼠乳腺肿瘤中，pVEGFR2和pAKT1的蛋白表达降低，显示出肿瘤消退和抗血管生成能力。在计算机上的研究还显示，莫纳可林X与VEGFR2活性位点中的关键氨基酸Cys 919结合的能力表明它是有效的VEGFR2抑制剂。

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