Inhibition of functional chemokine receptor CXCR4 reduces the production of IL-8 and VEGF by malignant human glioma cells.

A109

Chemokine receptor CXCR4 plays an important role in tumor growth, angiogenesis and metastasis. In our previous studies, Nordy, a synthesized chiral compound of nordihydroguaiaretic acid, has been shown to inhibit tumor growth and angiogenesis of various cancers. However, the effect of Nordy on CXCR4 expression in cancers is unclear. The objective of this study was to determine the potential effect of Nordy on CXCR4 expression and function in human glioblastoma cell line U87. We examined the inhibitory effect of Nordy on CXCR4 by examining CXCR4 expression on U87 cells treated with Nordy. We also detected the effect of Nordy on CXCR4 function by analysis for the changes of CXCR4-induced IL-8 and VEGF production after Nordy treatment. We observed that Nordy could not only significantly decrease functional CXCR4 expression but also inhibit CXCR4-mediated IL-8 and VEGF production at both protein and mRNA levels. Our data suggest that Nordy can inhibit tumor angiogenesis practically by decreasing CXCR4 expression and blocking CXCR4 function.