Background and objective: Canstatin is a newly discovered endogenous inhibitor of angiogenesis. Previous study has shown that canstatin can efficiently suppress the growth of human cancers, even more potent than endostatin. This study was to investigate the antitumor effects of canstatin gene on human esophageal carcinoma xenografts.
Methods: Tumor xenografts were induced with KYSE150 cells in BALB/c nude mice, and randomized into three groups: PBS, adenovirus green fluorescent protein (Ad-GFP), and Ad-GFP-canstatin groups. During treatment, tumor size was measured. The mice were killed 30 days later to observe tumor morphology. The expression of vascular endothelial growth factor (VEGF), fetal liver kinase-1 (Flk-1), caspase-3 and microvessel density (MVD) were detected by immunohistochemistry.
Results: Compared with that in Ad-GFP and PBS groups, tumor growth in Ad-GFP-canstatin group was significantly suppressed in the first week after gene transfection. The inhibition rate of tumor growth was up to 61% at the sixth day. Necrotic regions were observed in all groups, especially in Ad-GFP-canstatin group. Compared with those in Ad-GFP and PBS groups, caspase-3 expression in Ad-GFP-canstatin group was higher (P<0.05), while Flk-1 expression and MVD was lower (P<0.05). There was no obvious difference in VEGF expression among the three groups.
Conclusion: Canstatin can inhibit the growth of human esophageal carcinoma by suppressing angiogenesis via down-regulating Flk-1 expression.