Intravital Microscopic Characterization of Suramin Effects in an Orthotopic Immunocompetent Rat Model of Pancreatic Cancer

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.