Suramin Inhibits Not Only Tumor Growth and Metastasis but Also Angiogenesis in Experimental Pancreatic Cancer |
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Authors: | Sarah Bhargava Birgit Hotz O Joe Hines Howard A Reber Heinz J Buhr Hubert G Hotz |
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Institution: | (1) Department of Surgery, Charité - Medical School Berlin, Campus Benjamin Franklin, Hindenburgdamm 30, 12200 Berlin, Germany;(2) Department of Surgery, UCLA School of Medicine, Los Angeles, CA, USA |
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Abstract: | Suramin inhibits the proliferation of several human tumors in vivo and in vitro. In this study, the effects of Suramin on
proliferation and angiogenesis were investigated in human pancreatic cancer cell lines and in an orthotopic nude mouse model
of human pancreatic cancer. The effects of Suramin on proliferation, viability, cell cycle, and apoptosis were studied in
five human pancreatic cancer cell lines. Suramin inhibited the proliferation of pancreatic cancer cells in a dose-dependent
manner and reduced viability at high concentrations. Cell cycle analysis revealed a decreased S-phase fraction in most cell
lines, whereas the apoptotic fraction was not notably different. In vivo treatment with Suramin significantly reduced pancreatic
tumor size (MiaPaCa-2, −74%; AsPC-1, −41%; and Capan-1, −49%) and metastatic spread (MiaPaCa-2, −79%; AsPC-1, −34%; and Capan,
−38%). As a parameter for angiogenic activity, vascular endothelial growth factor (VEGF) secretion was measured, revealing
reduced VEGF concentrations under Suramin treatment in both cell culture medium and ascites. Also, microvessel density quantified
in primary tumors was reduced in animals treated with Suramin. Therefore, Suramin inhibits the proliferation of human pancreatic
cancer in vitro and in vivo. The therapeutic effects seem to involve cell cycle kinetics and may be in part related to the
antiangiogenic action of the drug.
Supported by the R.S. Hirshberg Foundation and the Deutsche Forschungsgemeinschaft (Grant HO 1843/2-1 & 1843/3-1). |
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Keywords: | Suramin Pancreatic cancer Angiogenesis Orthotopic mouse model Microvessel density |
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