ACTIBIND, an actin-binding fungal T2-RNase with antiangiogenic and anticarcinogenic characteristics
ACTIBIND, an actin-binding fungal T2-RNase with antiangiogenic and anticarcinogenic characteristics
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DOI：
10.1002/cncr.21878
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发表时间：
2006-05-15
期刊：
影响因子：
6.2
通讯作者：
Shoseyov, O
中科院分区：
文献类型：
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作者：
Roiz, L;Smirnoff, P;Shoseyov, O
背景ACTIBIND是一种具有肌动蛋白结合活性的尼日尔细胞外核糖核酸酶（T-2-核糖核酸酶[RNase]）。在植物中，ACTIBIND通过干扰细胞内肌动蛋白网络来抑制花粉管的伸长并改变其方向。问题是Actibind是否也能影响哺乳动物的癌症发展。在存在或不存在1 μ M ACTIBIND的情况下，在人结肠癌（HT-29、Caco-2、RSB）、乳腺癌（ZR-75-1）和卵巢癌（2780）细胞中进行细胞集落形成。在HT-29和ZR-75-1细胞中，通过显微镜观察和Matrigel侵袭试验研究了Actibind油细胞迁移的影响。在血管生成素或碱性成纤维细胞生长因子（bFGF）（各1 μ g/mL）存在下，在人脐静脉内皮细胞（HUVEC）中，用1或10 AM的ACTIBIND孵育过夜后，评估管形成。在无胸腺小鼠异种移植模型中，皮下注射HT-29细胞，随后皮下（0.4-8 mg/小鼠/注射）或腹膜内（0.001-1 mg/小鼠/注射）注射爱替宾。在大鼠二甲肼（DMH）-结直肠癌发生模型中，通过渗透微泵（250 μ g/大鼠/天）或通过微胶囊（1.6 mg/大鼠/天）经口给药，将爱替宾直接释放至结肠。检查异常隐窝病灶、远端结肠肿瘤和肿瘤血管。爱替宾具有与其核糖核酸酶活性无关的抗克隆形成作用。它还以剂量反应性方式抑制血管生成素诱导的HUVEC管形成。发现ACTIBIND在体外与肌动蛋白结合。它还与癌细胞表面结合，导致内部肌动蛋白网络破坏，并通过Matrigel涂层过滤器抑制细胞运动性和侵袭性。在小鼠中，通过皮下或腹膜内给药，爱替宾可抑制HT-29异种移植肿瘤的发展。对DMH诱发的大鼠结肠肿瘤有预防和治疗作用。它还降低了肿瘤观察的程度。本研究表明，爱替宾是一种有效的抗血管生成和抗癌因子。
BACKGROUND. ACTIBIND is an Aspergillus niger extracellular ribonuclease (T-2-ribonuclease [RNase]) that possesses actin-binding activity. In plants, ACTIBIND inhibits the elongation and alters the orientation of pollen tubes by interfering with the intracellular actin network. The question rose whether ACTIBIND can also affect mammalian cancer development.METHODS. Cell colony formation was performed in human colon (HT-29, Caco-2, RSB), breast (ZR-75-1), and ovarian (2780) cancer cells in the presence or absence of 1 mu M ACTIBIND. In HT-29 and ZR-75-1 cells, the effect of ACTIBIND oil cell migration was studied by microscopic observations and by invasion assay through Matrigel. Tube formation was assessed in human umbilical vein endothelial cells (HUVEC) in the presence of angiogenin or basic fibroblast growth factor (bFGF) (1 mu g/mL each) following overnight incubation with 1 or 10 AM ACTIBIND. In an athymic mouse xenograft model, HT-29 cells were injected subcutaneously, followed by subcutaneous (0.4-8 mg/mouse/injection) or intraperitoneal (0.001-1 mg/mouse/injection) injections of ACTIBIND. In a rat dimethylhydrazine (DMH)-colorectal carcinogenesis model, ACTIBIND was released directly into the colon via osmotic micropumps (250 mu g/rat/day) or given orally via microcapsules (1.6 mg/rat/day). Aberrant crypt foci, tumors in the distal colon, and tumor blood vessels were examined.RESULTS. ACTIBIND had an anticlonogenic effect unrelated to its ribonuclease activity. It also inhibited angiogenin-induced HUVEC tube formation in a dose-responsive manner. ACTIBIND was found to bind actin in vitro. It also bound to cancer cell surfaces, leading to disruption of the internal actin network and inhibiting cell motility and invasiveness through Matrigel-coated filters. In mice, ACTIBIND inhibited HT-29 xenograft tumor development, given either as a subcutaneous or intraperitoneal treatment. In rats, ACTIBIND exerted preventive and therapeutic effects oil developing colonic tumors induced by DMH. It also reduced the degree Of tumor observation.CONCLUSIONS. This study indicated that ACTIBIND is an effective antiangiogenic and anticarcinogenic factor.