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磷脂可减少大鼠结肠肿瘤细胞的腹腔内粘连以及体外对细胞外基质的粘连。

Phospholipids reduce the intraperitoneal adhesion of colonic tumor cells in rats and adhesion on extracellular matrix in vitro.

作者信息

Jansen Marc, Treutner Karl-Heinz, Jansen Petra Lynen, Otto Jens, Schmitz Britta, Mueller Stefan, Weiss Claudia, Tietze Lothar, Schumpelick Volker

机构信息

Department of Surgery, University Clinic Aachen, Pauwelsstrasse 30, 52057 Aachen, Germany.

出版信息

Int J Colorectal Dis. 2004 Nov;19(6):525-32. doi: 10.1007/s00384-004-0611-7. Epub 2004 Aug 12.

Abstract

OBJECTIVE

To evaluate the influence of intraperitoneal treatment with phospholipids on the formation of peritoneal carcinosis after inoculation of colonic tumor cells in rats. The presence of tumor cells in the peritoneal cavity serves as a prognostic marker for postoperative survival after resection of gastrointestinal cancer. Intraperitoneal tumor cell attachment is a pivotal step in developing peritoneal carcinosis. Intraabdominal application of phospholipids resulted in a significant decrease of adhesion formation, especially at sites of peritoneal lesions.

METHODS

2x10(6) colonic tumor cells (DHD/K12/TRb) were injected intraperitonely in female BD-IX rats. A total of 90 rats were divided into three groups with treatments of phospholipids at 75 mg/kg or 150 mg/kg bodyweight or sodium chloride at 0.9% in the control group. The treatment groups were subdivided into animals with defined peritoneal lesions and animals without lesions. After 30 days, the extent of peritoneal carcinosis was determined by measuring the tumor volume, the area of tumor attachment and the Peritoneal Cancer Index. Over a 90-day observation period, the survival rate was analyzed. In vitro, we examined the reduction of tumor cell adhesion on extracellular matrix components after treatment with phospholipids. Microtiter plates were coated with laminin, fibronectin or collagen IV for adhesion experiments.

RESULTS

In our study, we found a significant reduction of peritoneal dissemination with respect to all evaluation methods after treatment with phospholipids at 150 mg/kg in animals without peritoneal lesions. This could not be achieved using the lower concentration of phospholipids (75 mg/kg). In vitro, the maximum reductions of tumor cell adhesion by phospholipids compared with the control values for laminin and fibronectin were 46% and 37%, respectively, whereas for collagen IV the reduction was only 24% ( p<0.0001).

CONCLUSIONS

A new method of prevention of intraperitoneal tumor cell adhesion, possibly leading to a reduced incidence of peritoneal carcinosis after surgery of gastrointestinal tumors, is introduced.

摘要

目的

评估磷脂腹腔内治疗对大鼠接种结肠肿瘤细胞后腹膜癌形成的影响。腹腔内存在肿瘤细胞是胃肠道癌切除术后生存的预后标志物。腹腔内肿瘤细胞附着是腹膜癌发生发展的关键步骤。腹腔内应用磷脂可显著减少粘连形成,尤其是在腹膜病变部位。

方法

将2×10⁶结肠肿瘤细胞(DHD/K12/TRb)腹腔内注射到雌性BD-IX大鼠体内。总共90只大鼠分为三组,分别用75mg/kg或150mg/kg体重的磷脂处理,对照组用0.9%的氯化钠处理。治疗组又分为有明确腹膜病变的动物和无病变的动物。30天后,通过测量肿瘤体积、肿瘤附着面积和腹膜癌指数来确定腹膜癌的程度。在90天的观察期内,分析生存率。在体外,我们检测了磷脂处理后肿瘤细胞在细胞外基质成分上的粘附减少情况。用层粘连蛋白、纤连蛋白或IV型胶原包被微量滴定板进行粘附实验。

结果

在我们的研究中,我们发现对于无腹膜病变的动物,用150mg/kg磷脂处理后,所有评估方法的腹膜播散均显著减少。使用较低浓度的磷脂(75mg/kg)无法达到这一效果。在体外,与层粘连蛋白和纤连蛋白的对照值相比,磷脂对肿瘤细胞粘附的最大减少率分别为46%和37%,而对于IV型胶原,减少率仅为24%(p<0.0001)。

结论

引入了一种预防腹腔内肿瘤细胞粘附的新方法,这可能会降低胃肠道肿瘤手术后腹膜癌的发生率。

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