[Inhibitory effects of cyclooxygenase-2 inhibitor celecoxib on growth and angiogenesis of human liver cancer HepG2 cell xenografts in small nude mice].
OBJECTIVE
Cyclooxygenase-2 (COX-2) is closely correlated to genesis of tumors, particularly digestive tract tumors, and its inhibitor has antitumor effect. This study was to investigate the inhibitory effects of COX-2 inhibitor celecoxib on growth and angiogenesis of human liver cancer HepG2 cell xenografts in small nude mice.


METHODS
HepG2 cells were transplanted into the dorsal subcutaneous tissue of athymic nude mice. The mice were treated with celecoxib 4 days after transplantation, and were killed 58 days later. Tumor volume and weight were measured. The expression of COX-2, vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and angiopoietin-2 (Ang-2) were detected by immunohistochemistry and reverse transcription-polymerase chain reaction (RT-PCR), and microvessel density (MVD) was observed by immunohistochemistry.


RESULTS
The average tumor volume was significantly smaller and the average tumor weight was significantly lighter in celecoxib group than in control group [(709.11+/-108.53) mm3 vs. (1,417.55+/-69.50) mm3, and (2.63+/-0.34) g vs. (5.32+/-0.98) g, P<0.01]. The inhibitory rate of tumor growth was 55.21%. The expression levels of COX-2, VEGF, bFGF and Ang-2, and MVD were significantly lower in celecoxib group than in control group (2.43+/-0.29 vs. 4.50+/-0.25, 2.80+/-0.30 vs. 5.49+/-0.58, 2.23+/-0.41 vs. 4.03+/-0.47, 2.88+/-0.25 vs. 5.53+/-0.54, and 29.27+/-1.52 vs. 128.24+/-9.82, P<0.01, respectively). COX-2 expression was positively correlated to VEGF, bFGF and Ang-2 expression and MVD (r=0.862, r=0.882, r=0.857, r=0.837,P<0.01, respectively).


CONCLUSIONS
Celecoxib inhibits the growth and angiogenesis of HepG2 cell xenografts in nude mice effectively via suppressing the expression of COX-2.
Zuo
Chao-Hui
CH
Department of General Surgery, Hunan Provincial Tumor Hospital, Changsha, Hunan 410013, P. R. China. zuochaohui@vip.sina.com
Li
Zu-Rong
ZR
Zhou
Xiao
X
Ouyang
Yong-Zhong
YZ
Zhou
Zheng-Yu
ZY
Zeng
Liang
L
D042702:Angiopoietin-2 / Q000096:biosynthesis / Q000235:genetics; D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000098:blood supply / Q000378:metabolism / Q000473:pathology; D000068579:Celecoxib; D045744:Cell Line, Tumor; D051546:Cyclooxygenase 2 / Q000096:biosynthesis* / Q000235:genetics; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology*; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D008113:Liver Neoplasms / Q000098:blood supply / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic / Q000473:pathology; D011720:Pyrazoles / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D011897:Random Allocation; D013449:Sulfonamides / Q000494:pharmacology*; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis / Q000235:genetics; D023041:Xenograft Model Antitumor Assays
D042702:Angiopoietin-2; D052246:Cyclooxygenase 2 Inhibitors; D011720:Pyrazoles; D012333:RNA, Messenger; D013449:Sulfonamides; D042461:Vascular Endothelial Growth Factor A; D016222:Fibroblast Growth Factor 2; D051546:Cyclooxygenase 2; D000068579:Celecoxib