Intravital microscopic characterization of suramin effects in an orthotopic immunocompetent rat model of pancreatic cancer.

Abstract

OBJECTIVES:

We investigated the effect of suramin on tumor growth and spread in an immunocompetent, orthotopic rat model of pancreatic cancer and analyzed the tumor vasculature by intravital microscopy.

METHODS AND METHODS:

In vitro, rat ductal pancreatic cancer cells (DSL-6A) were incubated with suramin (10-800 microg/ml), and cell proliferation was assessed. In vivo, DSL-6A tumors were induced in the pancreas of Lewis rats. Animals received suramin (60 mg/kg, weekly i.p.) or the vehicle (controls). Treatment started after 3 days. Intravital microscopy after 1, 4, and 8 weeks quantified diameter, density, and permeability of tumor vessels. Primary tumor volume, local infiltration, and metastatic spread were determined at autopsy. Microvessel density was analyzed by immunohistochemistry.

RESULTS:

In vitro, proliferation was inhibited by suramin up to 95%. In vivo, all controls developed extensive tumor growth and spread. No tumor was detectable in half of the suramin-treated animals after 8 weeks; tumor dissemination was almost completely depressed. Suramin therapy resulted in a complete regression of tumor macrovessels and a significant reduction of microvessel density.

CONCLUSION:

Suramin significantly reduces primary tumor growth and dissemination in a clinically relevant rat model of pancreatic cancer and seems to play an important role for the inhibition of tumor angiogenesis.

• Authors: Birgit Hotz, Heinz J Buhr, Hubert G Hotz
• Journal: Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract (J Gastrointest Surg) Vol. 12 Issue 5 Pg. 900-6 (May 2008) ISSN: 1091-255X [Print] United States
• PMID: 18320288 (Publication Type: Journal Article)

Chemical References

• Angiogenesis Inhibitors
• Antineoplastic Agents
• Suramin

Topics

• Angiogenesis Inhibitors (therapeutic use)
• Animals
• Antineoplastic Agents (pharmacology, therapeutic use)
• Capillary Permeability (drug effects)
• Carcinoma, Pancreatic Ductal (blood supply, drug therapy, pathology)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Microcirculation (drug effects)
• Microscopy, Video
• Neoplasm Transplantation
• Pancreatic Neoplasms (blood supply, drug therapy, pathology)
• Rats
• Rats, Inbred Lew
• Suramin (pharmacology, therapeutic use)
• Tumor Cells, Cultured