Zuo Chao-Hui, Li Zu-Rong, Zhou Xiao, Ouyang Yong-Zhong, Zhou Zheng-Yu, Zeng Liang
Department of General Surgery, Hunan Provincial Tumor Hospital, Changsha, Hunan 410013, P. R. China.
Ai Zheng. 2006 Apr;25(4):414-20.
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.
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.
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).
Celecoxib inhibits the growth and angiogenesis of HepG2 cell xenografts in nude mice effectively via suppressing the expression of COX-2.
环氧化酶-2（COX-2）与肿瘤的发生密切相关，尤其是消化道肿瘤，其抑制剂具有抗肿瘤作用。本研究旨在探讨COX-2抑制剂塞来昔布对人肝癌HepG2细胞裸鼠移植瘤生长和血管生成的抑制作用。
将HepG2细胞接种于裸鼠背部皮下组织。移植后4天用塞来昔布处理小鼠，58天后处死。测量肿瘤体积和重量。采用免疫组织化学和逆转录-聚合酶链反应（RT-PCR）检测COX-2、血管内皮生长因子（VEGF）、碱性成纤维细胞生长因子（bFGF）和血管生成素-2（Ang-2）的表达，免疫组织化学观察微血管密度（MVD）。
塞来昔布组平均肿瘤体积明显小于对照组[（709.11±108.53）mm3对（1417.55±69.50）mm3]，平均肿瘤重量明显轻于对照组[（2.63±0.34）g对（5.32±0.98）g，P<0.01]。肿瘤生长抑制率为55.21%。塞来昔布组COX-2、VEGF、bFGF和Ang-2的表达水平及MVD均明显低于对照组（2.43±0.29对4.50±0.25、2.80±0.30对5.49±0.58、2.23±0.41对4.03±0.47、2.88±0.25对5.53±0.54、29.27±1.52对128.24±9.82，P均<0.01）。COX-2表达与VEGF、bFGF和Ang-2表达及MVD呈正相关（r分别为0.862、0.882、0.857、0.837，P<0.01）。
塞来昔布通过抑制COX-2的表达有效抑制裸鼠HepG2细胞移植瘤的生长和血管生成。
