塞来昔布对人肝癌细胞增殖的抑制作用

Inhibitory effects of cyclooxygenase-2 inhibitor celecoxib on the proliferation of hepatocellular carcinoma cells

目的观察塞来昔布对肝癌增殖的抑制作用。方法以人肝癌细胞株SMMC-7721为研究对象,四唑氮蓝还原法(MTT)观察不同浓度和作用时间的塞来昔布对细胞增殖的抑制作用,流式细胞技术检测细胞周期,并用小鼠肝癌细胞株H22建立昆明鼠移植瘤模型,观察塞来昔布对移植瘤生长的抑制效果。结果MTT显示塞来昔布对人肝癌细胞SMMC-7721生长有显著的抑制作用,且呈现出时间和剂量依赖性;塞来昔布(40μmol/L)作用于SMMC-7721细胞36h后,G1期细胞比率由44.7%上升至49.9%,S+G2/M期细胞比率由55.4%下降至50.1%,细胞增殖受抑制。在体动物实验表明,塞来昔布对移植瘤的生长和局部转移有显著的抑制效果。结论环氧合酶-2抑制剂塞来昔布对不同来源的肝癌细胞株均有增殖抑制作用,可能是预防和治疗肝癌的重要候选药物之一。

Objective To study the inhibitory effects of celecoxib,a cyclooxygenase-2 inhibitor,on the proliferation of hepatocellular carcinoma cells.Methods The in vitro inhibitory effects of celecoxib at different concentrations and for different treatment time lengths on human liver cancer cell line SMMC-7721 were observed with MTT assay,and flow cytometry was performed to detect the cell cycle changes.The in vivo tumor inhibition effect of celecoxib was evaluated in Kunming mice bearing transplanted tumor derived from liver cancer cell line H22 transplantation.Results Celecoxib significantly inhibited the in vitro growth of human liver cancer cell line SMMC-7721 in a time-and dose-dependent manner.A 36-hour celecoxib treatment（40 μmol/L）resulted in decreased SMMC-7721 cell proliferation and an increase of the cell percentage in G1 phase from 44.7% to 49.9% with decreased cell percentage in S and G2/M phases from 55.4% to 50.1%.In the mice bearing H22 transplanted tumor,celecoxib showed significant inhibitory effect on the growth and local metastasis of the transplanted tumor.Conclusions Celecoxib can inhibit the proliferation of different liver cancer cell lines both in vitro and in vivo,and therefore may serve as an important candidate drug for prevention and treatment of hepatocellular carcinoma.