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


CONCLUSIONS
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.
Hotz
Birgit
B
Department of Surgery I, Charité-Medical School, Campus Benjamin Franklin, Hindenburgdamm 30, 12203 Berlin, Germany.
Buhr
Heinz J
HJ
Hotz
Hubert G
HG
D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002199:Capillary Permeability / Q000187:drug effects; D021441:Carcinoma, Pancreatic Ductal / Q000098:blood supply / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D008833:Microcirculation / Q000187:drug effects; D018715:Microscopy, Video; D009368:Neoplasm Transplantation; D010190:Pancreatic Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000473:pathology; D051381:Rats; D011917:Rats, Inbred Lew; D013498:Suramin / Q000494:pharmacology / Q000627:therapeutic use*; D014407:Tumor Cells, Cultured
D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D013498:Suramin