Liu Hua, Huang Peixin, Xu Xuanfu, Liu Jun, Guo Chuanyong
Department of Gastroenterology, The Tenth Hospital Affiliated to Tongji University, No. 301, Yanchang Road, 200072, Shanghai, People's Republic of China.
Dig Dis Sci. 2009 Jul;54(7):1418-24. doi: 10.1007/s10620-008-0510-9. Epub 2008 Oct 16.
Cyclooxygenase-2 (COX-2) inhibitors cause growth inhibition of human gastric carcinoma cells, but it remains unclear whether this is both COX-2 dependent and independent. The related mechanisms remain to be determined. Both low COX-2 expressing gastric carcinoma and high COX-2 expressing gastric carcinoma cells were used to study the effect and mechanisms of celecoxib on gastric carcinoma cell growth. Celecoxib resulted in comparable growth inhibition in AGS cells with stable transfections of small interfering RNA (siRNA) against COX-2 (SAC) and negative control vector (NC) cells. Simultaneously, celecoxib resulted in significant reduction of Bcl-2 and significant increase of p21(WAF1) and p27(KIP1) in SAC and NC cells. The present study shows that celecoxib causes growth inhibition of gastric carcinoma cells by decreasing Bcl-2 of cyclooxygenase-2-dependent pathway, and by increasing p21(WAF1) and p27(KIP1) of cyclooxygenase-2-independent pathway. These data extend our knowledge on the effect and mechanisms of celecoxib-induced inhibition of gastric carcinoma cell growth.
环氧化酶-2（COX-2）抑制剂可抑制人胃癌细胞的生长，但这种抑制是否依赖于COX-2以及是否存在非COX-2依赖的情况仍不清楚。相关机制有待确定。本研究使用低COX-2表达的胃癌细胞和高COX-2表达的胃癌细胞，来研究塞来昔布对胃癌细胞生长的影响及其机制。塞来昔布对稳定转染针对COX-2的小干扰RNA（siRNA）的AGS细胞（SAC）和阴性对照载体（NC）细胞的生长抑制作用相当。同时，塞来昔布使SAC和NC细胞中的Bcl-2显著降低，p21（WAF1）和p27（KIP1）显著增加。本研究表明，塞来昔布通过降低COX-2依赖途径的Bcl-2以及增加COX-2非依赖途径的p21（WAF1）和p27（KIP1）来抑制胃癌细胞的生长。这些数据扩展了我们对塞来昔布诱导胃癌细胞生长抑制的作用及机制的认识。
