Taurolidine inhibits tumor cell growth in vitro and in vivo
Taurolidine inhibits tumor cell growth in vitro and in vivo
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DOI：
10.1007/s10434-000-0685-6
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发表时间：
2000-10-01
影响因子：
3.7
通讯作者：
Redmond, HP
中科院分区：
文献类型：
--
作者：
McCourt, M;Wang, JH;Redmond, HP
背景：牛磺罗定是一种氨基酸牛磺酸的衍生物，具有抗内毒素、抗菌和抗粘附活性。我们假设，牛磺罗定可以抑制肿瘤细胞生长，在体外和体内设置。方法：在体外实验中，用5、10、15、25 μ g/ml的Taurolidine处理DHD/K12/TRb细胞，观察Taurolidine对DHD/K12/TRb细胞生长的影响。单独在培养基中孵育的细胞用作对照。使用市售技术测量细胞增殖、细胞活力、细胞死亡和细胞凋亡。在体内实验中，将艾德IX大鼠随机分为两组（n = 10/组）。A组（对照组）行开腹手术，腹腔内注入DHD/K12/TRb肿瘤细胞，然后注入磷酸盐缓冲液（PBS）。组B接受牛磺罗定（100 mg/kg）代替PBS。24天后处死动物，通过计数腹腔中肿瘤结节的数量来评估肿瘤负荷。用牛磺罗定孵育肿瘤细胞导致增殖率降低4倍（25 +/- 4% vs.对照组100 +/- 28%），LDH释放增加证明细胞坏死增加4倍（403 +/-28%对比对照组的100 +/-26%），牛磺罗定浓度为25 μ g/ml。还观察到细胞活力呈剂量依赖性降低。在体内研究中，局部牛磺罗定给药导致肿瘤负荷的显著降低（B组动物中3 +/-1个结节对A组动物中649 +/-101个结节）。
Background: Taurolidine, a derivative of the amino acid taurine, exhibits antiendotoxin, antibacterial, and antiadherence activity. We hypothesized that Taurolidine may inhibit tumor cell growth, both in an in vitro and in vivo setting. Our aim was to examine the effect of Taurolidine on the growth of a rat metastatic colorectal tumor cell line (DHD/K12/TRb) in vitro and in vivo.Methods: In the in vitro experiments, DHD/K12/TRb cells were incubated with 5, 10, 15, 25, mu g/ml of Taurolidine. Cells incubated in culture medium alone were used as controls. Cell proliferation, cell viability, cell death, and cell apoptosis were measured using commercially available techniques. In the in vivo experiment, ED IX rats were randomized into two groups (n = 10/group). Group A (control) underwent laparotomy and instillation of DHD/K12/TRb tumor cells intraperitoneally followed by phosphate buffered saline (PBS). Group B received Taurolidine (100 mg/kg) instead of PBS. Animals were killed after 24 days and tumor burden assessed by counting the number of tumor nodules in the peritoneal cavity.Results: Incubation of the tumor cells with Taurolidine resulted in a 4-fold decrease in proliferation rates (25 +/- 4% vs. 100 +/- 28% for controls) and a 4-fold increase in cell necrosis as demonstrated by the increase in LDH release (403 +/- 28% vs. 100 +/- 26% for controls), at a Taurolidine concentration of 25 mu g/ml. A dose-dependent decrease in cell viability was also observed. In the in vivo study, local Taurolidine administration resulted in significant decreases in tumor burden (3 +/- 1 nodules in Group B animals vs. 649 +/- 101 nodules in Group A animals).Conclusions: Taurolidine inhibits the growth of a rat metastatic colorectal tumor cell Line in vitro and in vivo and thus may have potential in the prevention of peritoneal metastases.