Influence of intraperitoneal application of taurolidine/heparin on expression of adhesion molecules and colon cancer in rats undergoing laparoscopy

J Surg Res. 2007 Jan;137(1):75-82. doi: 10.1016/j.jss.2006.07.013. Epub 2006 Nov 15.

Abstract

Background: Recent experimental studies have shown that intraperitoneal administration of taurolidine/heparin causes a reduction of local tumor growth after laparoscopy in rat models. It might be that the anti-adherent activities of these agents are responsible for this effect. In this study we investigated the adhesion molecules E-cadherin, beta1-integrin, and CD44.

Materials and methods: Following a 10,000 colon adenocarcinoma cells' (DHD/K12/TRb) intraperitoneal application a cecum resection and a partial parietal peritoneum resection (1 x 1 cm) were performed using a three trocar technique in 30 BD IX rats. After randomization in two groups, the cecum suture line and the parietal peritoneal defect were either lavaged with 1 mL of 0.5% taurolidine/10 IU heparin or with equal amounts of 0.9% normal saline solution. Rats were sacrificed four weeks after operation and total tumor growth was determined. E-cadherin, beta1-integrin, and CD44 were assessed immunohistochemically on the tumor tissue.

Results: The expression of E-cadherin was significantly reduced to 46.7% (complete loss of staining) in the taurolidine/heparin group. Although no significant difference was detected concerning the beta1-integrin and CD44 expression, a slightly reduced expression level with 26.7% of negative staining in metastases of the taurolidine/heparin group was observed. The total tumor weight (171.1 +/- 181.2 mg) as well as the total number of tumor lesions was also reduced by the substances compared to the control group (283.2 +/- 91.4 mg).

Conclusions: Taurolidine/heparin led to a significant reduction of local tumor growth. Additionally a reduction of the expression of E-cadherin was observed. However, the biological behavior of this molecule is multivariant, controversial and still unclear. Further studies should elucidate its role in the epithelial tumor genesis.

MeSH terms

  • Adenocarcinoma / drug therapy*
  • Adenocarcinoma / secondary
  • Adenocarcinoma / surgery*
  • Animals
  • Anticoagulants / pharmacology
  • Antineoplastic Agents / pharmacology*
  • Cadherins / genetics
  • Cell Adhesion Molecules / genetics*
  • Colonic Neoplasms / drug therapy*
  • Colonic Neoplasms / pathology
  • Colonic Neoplasms / surgery*
  • Combined Modality Therapy
  • Gene Expression Regulation, Neoplastic / drug effects
  • Heparin / pharmacology
  • Hyaluronan Receptors / genetics
  • Injections, Intraperitoneal
  • Integrin beta1 / genetics
  • Intestinal Mucosa / physiology
  • Laparoscopy
  • Male
  • Rats
  • Rats, Inbred Strains
  • Taurine / analogs & derivatives*
  • Taurine / pharmacology
  • Thiadiazines / pharmacology*

Substances

  • Anticoagulants
  • Antineoplastic Agents
  • Cadherins
  • Cell Adhesion Molecules
  • Hyaluronan Receptors
  • Integrin beta1
  • Thiadiazines
  • Taurine
  • taurolidine
  • Heparin