塞来昔布对实验性结肠癌原位移植瘤生长及血管形成的影响

目的:探讨塞来昔布对实验性结肠癌原位移植瘤生长及血管形成的影响。方法:使用对数生长期的人结肠癌细胞(HT-29)于裸鼠皮下接种成瘤后原位种植。术后随机分为对照组(C组)及塞来昔布高、中、低剂量组(H、M、L组)共四组进行研究。结果:24只裸鼠实验期间无1只死亡,成瘤率为100%,比较各组原位移植瘤体积和瘤质量差异有统计学意义,P值均<0·05。L、M和H组的抑瘤率分别为25·30%、38·80%和76·92%,与对照组比较差异有统计学意义,P=0·000,且存在明显的剂量依赖。干预组瘤组织中MVD、VEGFmRNA、MMP-2mRNA和匀浆上清中PGE2含量与对照组相比差异有统计学意义,P值分别为0·050、0·050、0·050和0·010,随着剂量增加,MVD、VEGFmRNA、MMP-2mRNA和匀浆上清中PGE2含量逐渐降低。瘤组织中PGE2含量与瘤质量,以及MVD与VEGFmRNA、MMP-2mRNA均存在显著的正相关性,r=0·8814,P=0·000;r=0·8573,P=0·000;r=0·6427,P=0·001。结论:塞来昔布通过抑制人结肠癌裸鼠原位移植瘤环氧化酶-2活性,抑制PGE2合成、VEGFmRNA和MMP-2mRNA表达,抑制肿瘤的血管形成,从而对结肠癌的生长有抑制作用。

Effect of celecoxib on growth and angiogenesis of orthotopic transplantation tumor of experimental colorectal cancer

OBJECTIVE:To investigate the effect of celecoxib on the growth and angiogenesis of orthotopic transplantation tumor of experimental colorectal cancer. METHODS: The cell line HT-29 in log phase of human colorectal cancer was implanted subcutaneously in nude mice and subsequently the subcutaneous implanted tumor was orthotopically implanted. Postoperatively these nude mice were randomly divided into four groups: control group (C), high dose(H), middle dose(M) and low dose groups(L) of celecoxib. RESULTS:None of the nude mice died and all nude mice formed the mass of colorectal tumor in situ, while the differences of the volume and the weight of tumor in situ were significant, P<0.05. The respective rates of the tumor inhibition of L group, M group and H group were 25.30%,38.80% and 76.92%, respectively and the differences compared with the control group were significant,P=0.000. The rate of the tumor inhibition was dose-dependent. The content of PGE_2 in tumor homogenate, MVD and the levels of VEGF mRNA and MMP-2 mRNA expressions in tumor tissue decreased gradually with the increase of celecoxib concentration. The content of the PGE_2 , MVD and the levels of VEGF mRNA and MMP-2 mRNA expressions in the treated-groups were significantly lower than those in the control,P=0.050,0.050,0.050 and 0.010 respectively. The content of the PGE_2 was correlated significantly with the weight of tumor in situ, r=0.881 4,P=0.000. MVD was closely related to the levels of VEGF mRNA and MMP-2 mRNA expressions in tumor tissue, r=0.857 3,P=0.000;r=0.642 7,P=0.001 respectively. CONCLUSIONS:Celecoxib can obviously inhibit the growth and angiogenesis of tumor by inhibiting the activity of COX-2, the synthesis of PGE_2 and the expressions of VEGF mRNA and MMP-2 mRNA in orthotopic transplantation tumor of human colorectal cancer in nude mice. [GK!4]