Lung cancer is the second most common cancer in men and women and is the leading cause of cancer related death in the USA. Docetaxel is an anti-microtubule agent used in the treatment of non-small cell lung cancer that may also have antiangiogenic properties. NRP-1 is a non tyrosine kinase docking receptor of vascular endothelial growth factor (VEGF165) and its overexpression is correlated with tumor angiogenesis. We hypothesize that docetaxel could inhibit angiogenesis in non-small cell lung cancer cell line and human umbilical vein endothelial cells (HUVEC) by decreasing the NRP-1 expression. CRL-5872, a non-small cell lung adenocarcinoma cell line, and HUVEC were treated with 1nM and 10nM Docetaxel for 48 hrs. We evaluated the expression of different angiogenesis related proteins like NRP-1, VEGF165 and PDGF-BB by Immuno-Western Blot analysis. We also explored the involvement of different signaling molecules, if any in regulation of NRP-1 expression. There is significant down regulation of NRP-1 in non small cell lung adenocarcinoma (CRL-5872) by 60% and human umbilical vein endothelial cells (HUVEC) by 40% with 10 nM Docetaxel as compared to untreated control. In similar conditions, docetaxel also significantly blocks PDGF-BB. The down regulation of NRP-1 is mediated through Akt pathway. Docetaxel is capable of inhibiting the expression of angiogenic factors including NRP-1 and PDGF-BB, through the inhibition of Akt signaling pathway. Thus, this study suggests that docetaxel inhibits an angiogenic switch in lung cancer.
This research work is supported by Midwest Biomedical Research Foundation.
98th AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA