选择性环氧合酶2抑制剂塞来昔布对人子宫内膜癌细胞的凋亡诱导  

Selective cyclooxygenase-2 inhibitor celecoxib induces the apoptosis of endometrial carcinoma cells

作　　者：房昭[1] 詹雪梅[1] 生秀杰[2] 杨爱莲[1] 

机构地区：[1]广东省江门市中心医院妇科,529070 [2]广州医学院附属第三医院妇产科

出　　处：《中华生物医学工程杂志》2010年第4期319-322,共4页Chinese Journal of Biomedical Engineering

摘　　要：目的研究环氧合酶2（COX-2）选择性抑制剂塞来昔布诱导入子宫内膜癌细胞凋亡作用。方法体外培养的人子宫内膜癌细胞HEC-1-B经塞来昔布处理后，采用Giemsa染色、流式细胞术和DNALadder观察HEC-1-B细胞凋亡变化；通过半定量RT．PCR方法检测HEC-1-B细胞COX．2及凋亡相关基因Fas、survivin的表达。结果20μmol／L塞来昔布处理HEC-1-B细胞后，Giemsa染色即可见细胞核固缩、碎裂，出现凋亡小体等细胞凋亡形态变化；流式细胞学检测示50μmol／L塞来昔布可使HEC－1-B细胞凋亡率达46．9％，PI荧光直方图出现凋亡细胞峰，DNA电泳可见典型的细胞凋亡梯形条带。塞来昔布处理HEC－1－B细胞后，COX－2mRNA表达下降，细胞凋亡相关基因Fas表达增加，细胞凋亡抑制基因survivin表达下降，50μmol／L塞来昔布可使survivin表达难以检出。结论塞来昔布对HEC－1-B细胞有明显的凋亡诱导作用，通过抑制COX－2表达进而使Fas表达上调，survivin表达下调可能是其诱导细胞凋亡机制之一。Objective To investigate the apoptosis- inductive effects of celecoxib, a selective inhibitor of cyclooxygenase-2 （COX-2） , on human endometrial carcinoma cells. Methods After treating human endometrial carcinoma cell HEC-1-B with celecoxib in vitro, apoptosis of HEC-1-B ceils was observed by Giemsa staining, flow cytometry and DNA ladder. Semi- quantitative RT- PCR was used to test the expression of COX-2, apoptosis-related Fas and survivin in HEC-1- B. Results Apoptotic morphological changes such as karyopyknosis, nuclear fragmentation and appearance of apoptotic bodies were noted by Giemsa staining after treating HEC-1- B cells with 20 μmol/L celecoxib. Flow cytometry analysis indicated apoptotic rate of HEC-1-B cells was as high as 46.9% after treated with 50 μmol/L celecoxib. Apoptotic peak was found in PI fluorescence histogram. Genome DNA electrophoresis further confirmed the formation of typical apoptotic DNA ladder. After HEC- 1 -B cells treated with celecoxib, the expression of COX-2 mRNA and apoptosis- related suppressor gene survivin declined, and expression of apoptosis- related gene Fas increased. 50 μmol/L celecoxib impeded detection of survivin expression. Conclusions Celecoxib induces apoptosis of HEC- 1B cells. By inhibiting COX-2 activity, the expression of Fas increases and survivin expression decreases, which may be one of the mechanisms of apoptosis induction.

关 键 词：子宫内膜肿瘤 细胞凋亡 抗肿瘤药 环氧合酶2 塞来昔布 

分 类 号：R737.33[医药卫生—肿瘤]