HUMAN UMBILICAL VEIN ENDOTHELIAL CELLS AND KS Y-1: USED IN VITRO TO EVALUATE ENDOTHELIAL CELL INHIBITION ACTIVITY OF COMPOUNDS

Abstract

KS Y-1 cells, an immortal AIDS associated Kaposi's sarcoma cell line, are reported to have cell surface markers consistent with activated vascular endothelial cells (Lunardi-Iskander et al, 1995). Because of these characteristics, they were evaluated to determine whether they can substitute for human umbilical vein endothelial cells (HUVECs) as a screen for inhibitors of endothelial cell proliferation. By inhibiting endothelial cell growth, the growth of new blood vessels in a tumor could be slowed or arrested thereby slowing or arresting the growth of the tumor. One hundred compounds were tested in vitro against both cell lines. When the GI50s for the two cell lines were compared, a correlation coefficient of 0.615 was obtained. However, removal of compounds with GI50s differing by more than a power of ten between the two cell lines produced a correlation coefficient of 0.945. With this in mind, an additional 500 compounds were tested against the KS Y-1 cells and compounds with a GI50 of 1uM or less were subsequently tested against the HUVECs. In total, 143 compounds were tested against both the HUVECs and the KS Y-1 cells. Comparisons of the GI50s for each compound against the KS Y-1 cells and the HUVECS produced a correlation coefficient of 0.65. Removing compounds with GI50s differing by more than a power of ten yielded a correlation coefficient of 0.88. The correlation coefficient for the excluded data set was —0.059. A modest correlation coefficient exists between KS Y-1 cells and HUVECS. However, exclusion of data points varying greater than ten fold gives a good correlation coefficient. When excluded data points are examined, it is obvious that KS Y-1 cells are more sensitive. This suggests KS Y-1 cells may be acceptable as a pre-screen for anti-HUVEC activity.