Song Yoo-Cheol, Kim Su-Hyeong, Juhnn Yong-Sung, Song Yong-Sang
Department of Obstetrics and Gynecology, Seoul National University College of Medicine, 28 Yongun-dong, Chongno-gu, Seoul, 110-744, Korea.
Ann N Y Acad Sci. 2007 Jan;1095:26-34. doi: 10.1196/annals.1397.004.
Celecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, induces the apoptosis in various cancers in COX-2 dependent and/or independent manners. The p53 protein is mutated in 50% of all human tumors and plays a key role in apoptosis, cell cycle, and the expression of several proteins. In ovarian cancer, the rate of p53 mutation has been shown to be very high and associated with poor prognosis. To explore the importance of functional status of p53 in apoptosis by celecoxib in ovarian cancer cells, the cellular response to celecoxib was determined in SK-OV3 ovarian cancer cells with null type p53 and PA-1 with wild-type p53. Our results showed that celecoxib inhibited cell growth more in PA-1 than in SK-OV3. The underlying antiproliferative mechanism may differ between these two cell types dependent upon the functional status of p53, which plays integral roles in regulating cell cycle and survival. Higher sub-G1 was shown in PA-1 than in SK-OV3 in response to celecoxib (PA-1 versus SK-OV3; 60.28% versus 6.69%). Caspase -8, -9, and -3 were activated in PA-1 cells, but not in SK-OV3 cells. These results suggest that death receptor and mitochondria-mediated apoptotic pathways may be involved in celecoxib-induced apoptosis dependent upon the functional status of p53. Our article demonstrated that the celecoxib effectively inhibited cell growth and induced apoptosis in human ovarian cancer cells with wild-type p53. Thus, apoptotic effect by celecoxib seemed to be different dependent upon the functional status of p53.
塞来昔布是一种选择性环氧化酶-2（COX-2）抑制剂，以COX-2依赖和/或独立的方式诱导多种癌症细胞凋亡。p53蛋白在所有人类肿瘤中有50%发生突变，在细胞凋亡、细胞周期以及几种蛋白质的表达中起关键作用。在卵巢癌中，p53突变率很高且与预后不良相关。为了探究p53功能状态在塞来昔布诱导卵巢癌细胞凋亡中的重要性，我们在p53基因缺失的SK-OV3卵巢癌细胞和p53基因野生型的PA-1细胞中测定了细胞对塞来昔布的反应。我们的结果显示，塞来昔布对PA-1细胞生长的抑制作用比对SK-OV3细胞更强。这两种细胞类型潜在的抗增殖机制可能因p53的功能状态不同而有所差异，p53在调节细胞周期和细胞存活中起着不可或缺的作用。与塞来昔布作用后，PA-细胞中出现更高比例的亚G1期细胞（PA-1与SK-OV3相比；60.28%对6.69%）。PA-1细胞中半胱天冬酶-8、-9和-3被激活，而SK-OV3细胞中未激活。这些结果表明，死亡受体和线粒体介导的凋亡途径可能参与了塞来昔布诱导的、依赖于p53功能状态的细胞凋亡。我们的研究表明，塞来昔布能有效抑制具有野生型p53的人卵巢癌细胞的生长并诱导其凋亡。因此，塞来昔布的凋亡作用似乎因p53的功能状态不同而有所差异。
