Abstract:
Eur J Clin Invest 2012; 42 (10): 10611067 Abstract Background Vascular endothelial growth factor (VEGF) helps control tumour growth via causing new capillaries growth in tumours. Four cardiac hormones [i.e. vessel dilator, long-acting natriuretic peptide (LANP), kaliuretic peptide (KP) and atrial natriuretic peptide (ANP)] that eliminate up to up to 86% of human small-cell lung cancers growing in mice were investigated for their effects on VEGF and the VEGFR2/KDR/Flk-1 receptor. The VEGFR2 receptor is the main receptor mediating VEGFs cancer-enhancing effects. Materials and Methods Four cardiac hormones were evaluated for their ability to decrease VEGF/VEGFR2 measured by ELISAs in three human cancer cell lines. Results Vessel dilator, LANP, KP and ANP, over a concentration range of 100 pM to 10 mu M, maximally decreased the VEGFR2 receptor in human pancreatic adenocarcinoma cells by 48%, 49%, 74% and 83%. Vessel dilator, LANP, KP and ANP decreased the VEGFR2 receptor by 77%, 89%, 88% and 67% in human small-cell lung cancer cells and by 48%, 92%, 64% and 71% in human prostate cancer cells. These results were confirmed with the cardiac hormones also decreasing the VEGFR2 receptor measured by Western blots. VEGF itself in pancreatic carcinoma cells was decreased by 42%, 58%, 36% and 40% by vessel dilator, LANP, KP and ANP. VEGF levels were decreased 25%, 23%, 17% and 23% in small-cell lung cancer cells and decreased by 24%, 20%, 23% and 24% in prostate cancer cells by vessel dilator, LANP, KP and ANP. Conclusion Four cardiac hormones are the first dual inhibitors of VEGF and the VEGFR2/KDR/Flk-1 receptor.
