Inhibitory Effects of Arsenic Trioxide and Thalidomide on Angiogenesis and Vascular Endothelial Growth Factor Expression in Leukemia Cells

摘要

Acute myeloid leukemia (AML) is a blood disorder characterized by uncontrolled proliferation of myeloidprogenitors and decrease in the apoptosis rate. The vascular endothelial growth factor (VEGF) promotes blood vesselregeneration which might play important roles in development and progression of neoplasia. Our previous studiesfocused on cytotoxicity and anticancer effects of arsenic trioxide (ATO) and thalidomide (THAL) as an anti-VEGFcompound in the AML cell model. ATO also affects regulatory genes involved in cell proliferation and apoptosis. Theaim of present study was to examine the effects of ATO and THAL alone and in combination on U937 and KG-1 cells, with attention to mRNA expression for VEGF isoforms. Growth inhibitory effects was assessed by MTT assay andapoptosis induction was determined by Annexin/PI staining. mRNA expression levels were evaluated by real-timePCR. Our data indicated that ATO (1.618μM and 1μM in KG-1 and U937 cell lines respectively), THAL (80μM and60μM) and their combination inhibited proliferation and induced apoptosis in our cell lines. mRNA expression ofVEGF (A, B) decreased while C and D isoforms did not show any significant changes. Taken together, according tothe obtained results, the VEGF autocrine loop could be a target as a therapeutic strategy for cases of AML.