Inhibitors of angiogenesis in surgical oncology efficacy in vitro versus efficacy in vivo

Background: Tumor angioneogenesis is stimulated by degradation products of the extracellular matrix, i.e. hyaluronic acid fragments. Methods and Results: We analyzed the cytostatic efficacy of apigenin, a pla nt flavenoid on calf pulmonary artery endothelial cells (CPAE) in the prese nce and absence of hyaluronic acid (HA) and hyaluronidase (H) and on the ca pillary formation by human micro vascular endothelial cells (HMEC) in a fib rin gel. Apigenin, at a concentration of 5 mu g/ml, inhibited the growth of CPAE by 75% (p < 0.05 to the control). At the same dose, apigenin completely blocke d the two-fold stimulation of CPAE-growth which resulted from the addition of KA (10 mu g/ml) and H (50 mu g/ml) to the culture medium. 5 mu g/ml apig enin inhibited capilllary formation in a fibrin gel by 80% as compared to t he control (p < 0.05). The direct cytostatic action of apigenin on colonic cancer cells was assayed on DHDK 12 cells from rats using the H, thymidine incorporation assay. The dose which inhibited the cell growth by 50% (ID50) was 8,6 mu g apigenin/ml. Finally, in syngenic BDIX rats, the efficacy of intraperitoneal injections of 50 mg/kg apigenin three times daily for nine days against liver tumors created by transplantation of DHDK 12 cells was t ested. Conclusion: Preliminary results indicate that such a treatment does not res ult in any reduction of the tumor size or the extent of intratumoral necros is and underline that for inhibitors of tumor neangiogenesis favorable in v itro data not necessarily corresponds with an efficacy in vivo.