Suramin hemmt das Wachstum des humanen Pankreaskarzinoms in vitro und in vivo

Abstract

Suramin, a polysulfonated naphthylurea compound, inhibits the proliferation of several human tumors in vitro and in vivo. The mechanisms of Suramin action include the inhibition of growth factor binding, an antiangiogenic effect and the inhibition of various nuclear enzymes. This study evaluates the effect of Suramin on proliferation, viability, cell cycle and apoptosis of human pancreatic cancer cells in vitro and in vivo growth in a clinically relevant orthotopic nude mouse model of pancreatic cancer. Cell cycle analysis revealed a decreased S-phase and an increased G0/G1-phase after Suramin treatment in 4 cell lines (Capan-2, PANC-1, MIAPaCa-2, AsPC-1), whereas the percentage of Capan-1-cells in S-phase was increased. High concentrations of Suramin increased the apoptotic fraction in all 5 cell lines, Suramin inhibited the proliferation of pancreatic cancer cells in a dose-dependent manner and reduced viability at high concentrations. The mechanisms of in vitro action of this antiproliferative drug seem to involve alterations of cell cycle kinetics and apoptosis. In vivo treatment with Suramin significantly reduced pancreatic tumor size and metastatic spread in an orthotopic nude mouse model.