The Anti-tumor Activity Of Indolin Small Molecular Compound Z24 And Its Anti-angiogenesis Activity

Angiogenesis, the sprouting of capillaries from preexisting blood vessels, is essential for the sustained growth of solid tumors. Tumors that lack adequate vasculature become necrotic and/or apoptotic and do not grow beyond a limited size. However, tumors that undergo neovascularization acquire the ability to enter a phase of rapid growth and generally exhibit increased metastatic potential. The significance of angiogenesis in the progression of human cancers has been highlighted by recent studies that relate angiogenic phenotype to patient survival. Thus, inhibiton of angiogenesis has been identified as an attractive approach for the treatment of human cancers. Among the anti-angiogenesis agents, indolin-2-ketone small compound SU5416, which is a selective inhibitor of the vascular endothelial growth factor (VEGF) receptor Flk-1/KDR, is a very prospective one and is currently in phase III clinical trials. In this study, we studied the anti-tumor activity of Z24, its antiangiogenesis activity, and its possible anti-angiogenesis mechanisms, which was a structural analog of SU5416.The results were as follows:1. Among the 64 indolin small molecular compounds, Z24 selectively inhibited the growth and survival of fetal bovine aorta endothelial cells (BEC), with IC₅₀ being 16.4μmol/L. While its inhibition to the growth of BEL-7402 in vitro was much lower, with IC50 being 106μmol/L, IC₅₀ to the human colon...