Investıgatıon of A new tyrosıne kınase ınhıbıtor of pazopanıb (gw786034) antı-angıogenıc effects on NON-SMAll cell lung cancer cell lıne (A549)

Lung cancer, although rare in the early twentieth century, today it's a major health problem that is rising in number of incidence. Non-small cell lung cancer (NSCLC) is a particularly aggressive type of cancer. Thanks to new and more efficient agents, new researches have been done nowadays. Balance of angiogenic and anti-angiogenic factors will bring new treatment ways to tumors like lung cancer. Activated tyrosine kinase receptor is responsible of signal transduction in cancer development that is composed of cell proliferation, tumor invasion and metastasis respectively. Pazopanib (GW786034) is inhibitor of tyrosine kinase receptors that are VEGFR-1,-2,-3, PDGFR and c-Kit. Recently, FDA clinically has approved usage of pazopanib against renal cell carcinoma (RCC). In this study, anti-angiogenic effects of tyrosine kinase inhibitor pazopanib were evaluated in vitro in human lung cancer cell line (A549) and human umbilical ven endothelial cell line (HUVEC). Cytotoxic effects of different pazopanib concentrations (2.5, 25, 50, 100, 200 µM) were determined by MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide) method. Antiproliferative effects were evaluated by real time cell analysis (RTCA DP) system according to changing in cell index values. ELISA was used to measured vascular endothelial growth factor (VEGF) and real-time PCR method was used to determined VEGF mRNA expression. Our results show that pazopanib depending on time and concentration decreases the amount of VEGF and cell proliferation due to invasion and migration in A549 and HUVEC cells. RTCA DP system results show that IC50 values of pazopanib at 24 hours was analyzed as 51.6 µM in A549 cells. As a result of our studies, pazopanib has important antiproliferative and anti-angiogenic effects on A549 cells according to results of HUVEC cells. It shows that pazopanib as a tyrosine kinase receptor inhibitor might be potential agent for lung cancer chemotherapy.