Alphastatin downregulates vascular endothelial cells sphingosine kinase activity and suppresses tumor growth in nude mice bearing human gastric cancer xenografts

Figure 1 Alphastatin inhibit HUVECs migration induced by HGF( crystatl violet stain, × 100). All data shown as mean ± SD. ^aP < 0.05; ^bP < 0.01 vs control group.

Figure 2 Alphastatin has no effect on HUVECs proliferation.

Figure 3 Alphastatin inhibit HUVECs tubule formation in response to PMA. All data shown as mean ± SD. ^aP < 0.05 vs control group.

Figure 4 Expression of SPK , EDG-1, EDG-3, EDG-5 in HUVECs.

Figure 5 Alphastatin downregulate HUVECs SPK activity in a dose-dependent manner. HUVECs SPK activity reached a minimum value at 6 h. All data shown as mean ± SD. A: ^aP < 0.05; ^bP < 0.01 vs 0 nmol/L alphastatin; B: ^aP < 0.05 vs 0 h group.

Figure 6 Alphastatin inhibit new capillaries formation on Matrigel plug (original magnification × 100). A: Many newly formed capillaries full of red blood cells (arrow); B: Granuloma formation without significant neovasculature.

Figure 7 Factor-VIII staining revealed decreased blood vessel density in alphastatin-treated group vs PBS group (× 400).

Figure 8 Animals injected with alphastatin exhibited a significantly reduced tumor volume. All data shown as mean ± SD. ^aP < 0.05; ^bP < 0.01 vs PBS group.