Suramin inhibits the growth of malignant mesothelioma in vitro, and in vivo, in murine flank and intraperitoneal models
Suramin inhibits the growth of malignant mesothelioma in vitro, and in vivo, in murine flank and intraperitoneal models
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DOI：
10.1016/s0169-5002(03)00363-5
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发表时间：
2003-12-01
期刊：
影响因子：
5.3
通讯作者：
Kaiser, LR
中科院分区：
文献类型：
--
作者：
Cook, JW;Sterman, DH;Kaiser, LR
恶性间皮瘤（MM）的手术减积最终因局部复发而失败。苏拉明，细胞外生长因子（ECGF）的抑制剂，已被证明在恶性间皮瘤的治疗在一个小的病例系列的疗效。我们的目标是研究生存的好处和疾病的进展，在几个MM动物模型治疗苏拉明作为一个潜在的药物辅助治疗。在有或没有苏拉明暴露的情况下，测量人（REN，1- 45）、大鼠（11-45）和鼠（AB 12）间皮瘤细胞的体外生长。将人和鼠MM肿瘤皮下植入鼠侧腹或腹膜内（i. p.）注入小鼠腹腔剂量和治疗方案进行了优化，以降低肿瘤进展的速度，并改善生存曲线。苏拉明抑制所有细胞系的体外生长，在苏拉明给药后三个倍增周期达到统计学显著性（P < 0.01），最大抑制为对照生长的10-25%。观察到显著的时间和剂量依赖性效应。在体内，苏拉明在异种模型中抑制MM的生长（对照生长的55%，P < 0.01），在同系模型中在低和高负荷剂量下抑制MM的生长（分别为对照生长的46%和36%，P < 0.01）。苏拉明处理抑制了REN腹膜内模型中的体内生长，通过比较处理和对照动物的当天死亡的尸检大体显示。较低的平均肿瘤负荷评分也反映了较高剂量的肿瘤抑制（对照组：4.0，高剂量组：3.4）。苏拉明在体外以时间和剂量依赖性方式抑制人、鼠和大鼠MM的生长。苏拉明还抑制免疫缺陷宿主体内人MM侧腹和腹膜内异种移植物的生长，以及免疫活性宿主中同基因小鼠侧腹肿瘤的生长。这些研究表明，苏拉明可能有潜力提供有效的治疗MM，进一步的研究是必要的，以阐明生存优势苏拉明介导的MM生长抑制。(C)2003爱思唯尔爱尔兰有限公司保留所有权利。
Surgical debulking of malignant mesothelioma (MM) ultimately fails due to local recurrence. Suramin, an inhibitor of extracellular growth factors (ECGFs), has demonstrated efficacy in the treatment of malignant mesothelioma in a small case series. Our goal was to study survival benefits and disease progression in several MM animal models treated with suramin as a potential agent for adjuvant therapy. In vitro growth of human (REN, 1-45), rat (11-45) and murine (AB12) mesothelioma cell tines were measured with or without suramin exposure. Human and murine MM tumors were implanted subcutaneously into murine flanks or injected intraperitoneally (i.p.) into murine abdominal cavities. Dose and treatment schedules were optimized to reduce the rate of tumor progression and to improve survival curves. Suramin inhibited the in vitro growth of all cell lines, reaching statistical significance (P < 0.01) three doubling cycles after suramin administration, with a maximum inhibition of 10-25% of control growth. A significant time- and dose-dependent effect was observed. In vivo, suramin inhibited the growth of MM in the xenogeneic model (55% of control growth, P < 0.01), and in the syngeneic model at both the low and high loading doses (46 and 36% of control growth, respectively, P < 0.01). Suramin treatment inhibited in vivo growth in the REN intraperitoneal model shown grossly by necropsy of same day deaths comparing treatment and control animals. Tumor inhibition with the higher dose was also reflected by the lower mean tumor burden scores (control: 4.0 and high dose: 3.4). Suramin inhibits the growth of human, murine, and rat MM in vitro, in a time- and dose-dependent manner. Suramin also inhibits the growth of human MM flank and intraperitoneal xenografts in vivo in an immunodeficient host, as well as the growth of syngeneic murine flank tumors in an immunocompetent host. These studies demonstrate that suramin may have the potential to provide effective therapy for MM, and that further studies are necessary to elucidate the survival advantage of suramin mediated MM growth inhibition. (C) 2003 Elsevier Ireland Ltd. All rights reserved.