目的：探讨环氧合酶2（cyclooxygenase2，COX2）抑制剂塞来昔布（celecoxib）诱导人肝癌细胞系SMMC7721凋亡的作用及其可能机制。方法：以10、25、50、75、100 μmol/L的塞来昔布处理SMMC7721细胞，MTT法检测肿瘤细胞增殖，Hoechst 33342/PI 双染法检测细胞凋亡的形态特征，流式细胞术检测细胞凋亡率和细胞周期变化。RTPCR法检测Fas和Bcl2mRNA的表达，Western blotting检测细胞Fas和Bcl2 蛋白的表达。结果：塞来昔布以剂量依赖的方式抑制SMMC7721细胞增殖。塞来昔布作用后，SMMC7721细胞出现核染色质凝集、核膜破裂等凋亡细胞典型的形态特征。25、50和100 μmol /L塞来昔布诱导SMMC7721细胞的凋亡率分别为(16.32±2.32)%、(38.05±2.47)%、(71.17±3.19)%，并使细胞阻滞于G0/G1期。塞来昔布处理后，SMMC7721细胞Fas mRNA及蛋白表达明显增强（P<0.01）；Bcl2 mRNA表达无明显变化（P>005），高浓度塞来昔布可下调Bcl2蛋白表达（P<0.01）。结论：塞来昔布能够抑制SMMC7721细胞增殖并诱导凋亡，其机制可能与影响凋亡相关基因表达有关。

Objective:To investigate the effect of COX2 inhibitor celecoxib on induction of apoptosis of hepatoma carcinoma SMMC7721 cell line and the possible mechanism. Methods: SMMC7721 cells were treated with 10, 25, 50, 75 and 100 μmol/L celecoxib; their proliferation was examined by MTT assay; typical apoptotic morphology was studied by Hoechst 33342/PI double staining; and cell cycle and apoptosis rate were detected by flow cytometry. Fas and Bcl2 mRNA expressions were examined by RTPCR, and their protein expressions were detected by Western blotting analysis. Results: Celecoxib dosedependently inhibited the growth of SMMC7721 cells. SMMC7721 cells showed typical apoptotic morphology features, such as nuclear chromatin condensation and nuclear membrane rupture, after celecoxib treatment. Apoptotic rates of SMMC7721 cells treated with 25, 50, and 100 μmol/L celecoxib were (16.32±2.32)%, (38.05±247)%, and (71.17±3.19)%, respectively;celecoxib induced cell cycle arrest of SMMC7721 cells in G0/G1 phase. Fas mRNA and protein expressions in celecoxibtreated SMMC7721 cells were higher than those in the untreated cells (P<001); the expression of Bcl2 mRNA was not affected by celecoxib stimulation (P>0.05), but Bcl2 protein expression was significantly downregulated (P<0.01). Conclusion：Celecoxib can inhibit the proliferation and induce apoptosis of SMMC7721 cells, possibly by regulating the expression of apoptosis related genes.

武警医学院博士启动基金课题（No. WBS200814）