选择性环氧合酶-2抑制剂塞来昔布对胃癌治疗作用的体内实验研究

目的探讨选择性环氧合酶-2(COX-2)抑制剂塞来昔布对体内胃癌生长的影响及作用机制。方法建立裸鼠胃癌模型,20只裸小鼠随机分为2组,对照组隔日腹腔注射生理盐水,塞来昔布组隔日腹腔注射塞来昔布30mg/kg,采用免疫组化法检测微血管密度(MVD),采用半定量-TRAP银染法检测端粒酶活性,流式细胞仪检测细胞周期、细胞凋亡率。结果塞来昔布组肿瘤生长明显受抑制,抑瘤率为61.3%,与对照组相比,差异有显著性(P<0.05);流式细胞仪检测到凋亡峰,细胞阻滞于G0/G1期。同时它也显著抑制胃癌细胞的端粒酶活性,肿瘤组织中的MVD较对照组显著降低。结论塞来昔布通过诱导细胞凋亡,降低端粒酶活性,减少血管生成,从而抑制胃癌生长。这可能是COX-2抑制剂塞来昔布体内抗胃癌的机制。

Study on the Effects of Selective COX-2 Inhibitor Celecoxib in Vivo in Gastric Cancer

Objective To study the effects of celecoxib,a selective COX-2 inhibitor,on gastric cancer in vivo and to explore its anti-neoplasm mechanism .Methods Twenty mice xenograft models with SGC-7901 human gastric cancer cell were established and randomly divided into two groups.The mice of treated groups were administered with selective COX-2 inhibitor celecoxib.The expression of CD 34 was examined by immunohistochemistry to evaluate microvessel density.Telomerase activity was detected by semi-TRAP assay.Flow cytometry was adopted to examine apoptotic rate and cell cycle .Results Celecoxib inhibited significantly the growth of xenograft and elevated the inhibiting rate(P<0.05) as compared with control grpups .The apoptotic peak was detected with FCM and cells were blocked in G_0/G_1 stage .The telomerase activity was significantly inhibited .Conclusion COX-2 inhibitor celecoxib has anticancer effects to gastric cancer in vivo by inducing apoptosis,inhibiting telomerase activity and reducing angiogenesis.We conclude that the results may indicate the mechanisms underlying the anti-cancer effect of COX-2 inhibitor.