[In vivo antitumor effect of canstatin gene on human esophageal carcinoma xenografts in nude mice].
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.


CONCLUSIONS
Canstatin can inhibit the growth of human esophageal carcinoma by suppressing angiogenesis via down-regulating Flk-1 expression.
Zheng
Xiang-Wei
XW
Department of Digestive Diseases, The Second Affiliated Hospital, Zhengzhou University, Zhengzhou, Henan, 450014, PR China.
Li
Yin
Y
Tang
Fu-Ai
FA
Ma
Jun
J
Zheng
Peng-Yuan
PY
Lu
Gao-Feng
GF
D020533:Angiogenesis Inhibitors / Q000235:genetics / Q000378:metabolism; D000818:Animals; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D024141:Collagen Type IV / Q000235:genetics* / Q000378:metabolism; D015536:Down-Regulation; D004938:Esophageal Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000628:therapy*; D005260:Female; D015316:Genetic Therapy; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D055806:Microvessels / Q000473:pathology; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic / Q000473:pathology; D011897:Random Allocation; D047368:Tumor Burden; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism*; D023041:Xenograft Model Antitumor Assays
D020533:Angiogenesis Inhibitors; C502625:COL4A2 protein, human; D024141:Collagen Type IV; D042461:Vascular Endothelial Growth Factor A; D040301:Vascular Endothelial Growth Factor Receptor-2; D053148:Caspase 3