Nestler G, Schulz H U, Schubert D, Krüger S, Lippert H, Pross M
Department of Surgery, Otto-von-Guericke University, Leipziger Strasse 44, D-39120, Magdeburg, Germany.
Surg Endosc. 2005 Feb;19(2):280-4. doi: 10.1007/s00464-003-9301-8. Epub 2004 Dec 9.
The object of this study was to examine the effect of taurolidine on intraabdominal tumor growth in a laparoscopic animal model. We tested the cytotoxic, antiadhesive, and anti-invasive effects of this substance on CC531 adenocarcinoma cells in vitro and in vivo using WAG rats.
For in vitro experiments, Transwell dual chambers with polycarbonate filters coated with 100 microg/cm2 Matrigel were used to investigate the effects of 5, 10, and 20 microl of 2.0% taurolidine on the invasion of 1 x 10(5) CC531 adenocarcinoma cells. For the adhesion assays, tumor cells were applied onto microtiter plates coated with 5, 10, and 20 microl taurolidine and 0.9% NaCl solution for the control group subsequently. For in vivo experiments, 40 WAG rats were randomized into three therapy groups and one control group. All animals underwent laparoscopy and received 1 ml of CC531 adenocarcinoma cells (5 x 10(6) cells/ml) intraabdominally at the beginning of the procedure. According to the randomization, the rats were administered taurolidine with different concentrations or 1 ml of 0.9% NaCl solution for the control group. After 21 days, the animals were killed and the intraabdominal tumor weight was determined.
For the in vitro experiments, we found a moderate cytotoxicity and a significant inhibition of tumor cell adhesion and invasion (p < 0.01) by all taurolidine concentrations used in the assay. For in vivo experiments, the application of all concentrations of taurolidine significantly decreased the intraperitoneal tumor weight (p < 0.001).
Taurolidine significantly decreases adhesion and invasion of CC531 adenocarcinoma cells in vitro and significantly diminishes tumor growth in vivo. This may offer additional therapeutic options for laparoscopic surgery for colorectal cancer.
本研究的目的是在腹腔镜动物模型中检测牛磺罗定对腹腔内肿瘤生长的影响。我们使用WAG大鼠在体外和体内测试了该物质对CC531腺癌细胞的细胞毒性、抗黏附及抗侵袭作用。
体外实验中，使用涂有100微克/平方厘米基质胶的聚碳酸酯滤膜Transwell双室，研究2.0%牛磺罗定的5、10和20微升剂量对1×10⁵个CC531腺癌细胞侵袭的影响。黏附实验中，将肿瘤细胞分别接种于涂有5、10和20微升牛磺罗定的微量滴定板以及涂有0.9%氯化钠溶液的微量滴定板上作为对照组。体内实验中，40只WAG大鼠随机分为三个治疗组和一个对照组。所有动物均接受腹腔镜检查，并在手术开始时腹腔内注射1毫升CC531腺癌细胞（5×10⁶个细胞/毫升）。根据随机分组，大鼠分别给予不同浓度的牛磺罗定或1毫升0.9%氯化钠溶液作为对照组。21天后，处死动物并测定腹腔内肿瘤重量。
体外实验中，我们发现所用的所有牛磺罗定浓度均具有中等细胞毒性，并能显著抑制肿瘤细胞的黏附与侵袭（p<0.01）。体内实验中，所有浓度的牛磺罗定应用均显著降低了腹腔内肿瘤重量（p<0.001）。
牛磺罗定在体外可显著降低CC531腺癌细胞的黏附与侵袭，在体内可显著抑制肿瘤生长。这可能为结直肠癌的腹腔镜手术提供额外的治疗选择。
