[Inhibitory effects of cyclooxygenase-2 inhibitor celecoxib on growth and angiogenesis of human liver cancer HepG2 cell xenografts in small nude mice].

ABSTRACT

BACKGROUND & 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.