McCourt M, Wang J H, Sookhai S, Redmond H P
Department of Surgery, Cork University Hospital, Ireland.
Ann Surg Oncol. 2000 Oct;7(9):685-91. doi: 10.1007/s10434-000-0685-6.
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.
In the in vitro experiments, DHD/K12/TRb cells were incubated with 5, 10, 15, 25, microg/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, BD 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.
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 microg/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).
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.
牛磺罗定是氨基酸牛磺酸的衍生物,具有抗内毒素、抗菌和抗黏附活性。我们推测牛磺罗定可能在体外和体内抑制肿瘤细胞生长。我们的目的是研究牛磺罗定对大鼠转移性结直肠肿瘤细胞系(DHD/K12/TRb)体外和体内生长的影响。
在体外实验中,将DHD/K12/TRb细胞与5、10、15、25微克/毫升的牛磺罗定孵育。仅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BD IX大鼠随机分为两组(每组n = 10)。A组(对照组)接受剖腹手术并经腹腔内注入DHD/K12/TRb肿瘤细胞,随后注入磷酸盐缓冲盐水(PBS)。B组接受牛磺罗定(100毫克/千克)而非PBS。24天后处死动物,通过计数腹腔内肿瘤结节数量评估肿瘤负荷。
在牛磺罗定浓度为25微克/毫升时,肿瘤细胞与牛磺罗定孵育导致增殖率降低4倍(对照组为100±28%,处理组为25±4%),乳酸脱氢酶释放增加表明细胞坏死增加4倍(对照组为100±26%,处理组为403±28%)。还观察到细胞活力呈剂量依赖性下降。在体内研究中,局部给予牛磺罗定导致肿瘤负荷显著降低(B组动物为3±1个结节,A组动物为649±101个结节)。
牛磺罗定在体外和体内均抑制大鼠转移性结直肠肿瘤细胞系的生长,因此可能在预防腹膜转移方面具有潜力。