摘要
背景:肝细胞癌(HCC)中有环氧合酶(COX)鄄2表达,非甾体抗炎药阿司匹林可能通过抑制COX鄄2的表达而抑制HCC生长。目的:比较3种选择性COX鄄2抑制剂美洛昔康、赛来昔布和罗非昔布对人肝癌细胞株SMMC鄄7721生长的影响,观察高选择性COX鄄2抑制剂罗非昔布对裸鼠HCC原位移植瘤生长的影响。方法:采用3H鄄胸腺嘧啶核苷(3H鄄TdR)掺入检测SMMC鄄7721细胞的DNA合成情况;采用免疫细胞化学染色检测增殖细胞核抗原(PCNA)的表达;采用DNA原位末端标记(TUNEL)染色检测细胞凋亡。给予HCC原位移植瘤裸鼠罗非昔布每日30mg/kg8周,测量肿瘤体积和重量。结果:美洛昔康、赛来昔布和罗非昔布均能显著抑制SMMC鄄7721细胞的3H鄄TdR掺入,其抑制作用呈剂量依赖性,50%抑制浓度(IC50)分别为8.55×10-8mol/L、1.22×10-8mol/L和6.27×10-9mol/L。3种选择性COX鄄2抑制剂(1×10-5mol/L)作用24h均可明显降低SMMC鄄7721细胞的PCNA表达,使细胞凋亡指数较对照组显著增高(14.6%±2.8%、21.6%±3.6%和27.1%±3.5%对1.0%±0.7%,P<0.01),COX鄄2抑制剂的选择性越高,凋亡指数也越高(P<0.01)。罗非昔布组裸鼠的HCC原位移植瘤显著小于对照组,体积抑瘤率和重量抑瘤率分别为73.2%和78.1%。结论:3种选择性COX鄄2抑制剂均能在体外有效抑制SMMC鄄7721细胞的生?
Background: Expression of cyclooxygenase(COX)-2can be detected in the hepatocellular carcinoma(HCC).Aspirin,a non-steroidal anti-inflammatory drug,can inhibit the growth of HCC probably through the inhibition of COX-2expression.Aims:To compare the effects of three kinds of selective COX-2inhibitors(meloxicam,celecoxib and rofecoxib)on the growth of human liver cancer cell line SMMC-7721,and to observe the effect of rofecoxib,a highly selective COX-2inhibitor,on the growth of HCC implanted in the liver of nude mice.Methods:The DNA synthesis of SMMC-7721cells was determined by 3 H-thymidine( 3 H-TdR)incorporation method.The expression of proliferating cell nuclear antigen(PCNA)was detected by immunocytochemistry.The terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling(TUNEL)assay was used to detect cell apoptosis.Rofecoxib(30mg/kg per day)was administered to HCC implanted nude mice for eight weeks,the volume and weight of the xenografts in situ were measured.Results: Meloxicam,celecoxib and rofecoxib could decrease the 3 H-TdR incorporation significantly in a dose-dependent manner in SMMC-7721cells.Their50%inhibitory concentration(IC 50 )were8.55×10 -8 mol/L,1.22×10 -8 mol/L and6.27×10 -9 mol/L,respectively.After treated with the above three selective COX-2inhibitors(1×10 -5 mol/L)for24hours,the expression of PCNA in SMMC-7721cells were decreased,and the apoptosis index was significantly increased compared with that of the controls(14.6%±2.8%,21.6%±3.6%and27.1%±3.5%vs.1.0%±0.7%,P<0.01).The higher the selectivity of COX-2,the higher the apoptosis index(P<0.01).The xenografts in situ in nude mice treated with rofecoxib were significantly smaller than those of the controls,and the inhibition rates were73.2%in volume and78.1%in weight. Conclusions:All three kinds of selective COX-2inhibitors can effectively inhibit the growth of SMMC-7721cells in vitro in proportion to their selectivity. The inhibition of HCC growth in vivo by rofecoxib suggests it may be an effective drug in the treatment of HCC.
出处
《胃肠病学》
2004年第1期5-8,共4页
Chinese Journal of Gastroenterology
基金
国家杰出青年科学基金(No.39725012)资助
