Celecoxib exhibits the greatest potency amongst cyclooxygenase (COX) inhibitors for growth inhibition of COX-2-negative hematopoietic and epithelial cell lines.
Celecoxib exhibits the greatest potency amongst cyclooxygenase (COX) inhibitors for growth inhibition of COX-2-negative hematopoietic and epithelial cell lines.
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发表时间：
2002-04
期刊：
影响因子：
11.2
通讯作者：
C. Waskewich;R. Blumenthal;Honglan Li;R. Stein;D. Goldenberg;J. Burton
中科院分区：
文献类型：
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作者：
C. Waskewich;R. Blumenthal;Honglan Li;R. Stein;D. Goldenberg;J. Burton
环氧合酶-2（考克斯-2）是治疗和/或预防炎症性疾病和癌症的重要细胞靶点。选择性考克斯-2抑制剂的出现现在允许更精确和更安全的治疗方法。对一系列癌细胞系进行考克斯-2选择性和非选择性抑制剂（包括塞来昔布（Celebrex）和罗非昔布（Vioxx））生长抑制作用的筛选，产生了两个意外的发现。首先，塞来昔布对造血和上皮癌细胞系的抗增殖作用非常相似。逆转录-PCR检测结果显示，大多数造血细胞系均不表达考克斯-2，无考克斯-2蛋白表达。此外，发现考克斯-2阴性上皮细胞系对塞来昔布的IC 50与其考克斯-2+对应物非常相似。因此，观察到重要的抗增殖作用，其独立于细胞谱系和考克斯-2状态。其次，还观察到考克斯-2抑制剂药物塞来昔布和罗非昔布对炎症适应症具有相似的考克斯-2选择性和临床疗效，但它们对癌细胞系的体外抗增殖作用显著不同。在整个细胞系组中观察到塞来昔布的IC 50为35-65 μ M。最后，细胞毒性的模式或程度在细胞系之间没有明显差异，因为在用塞来昔布处理后，在考克斯-2+和-阴性细胞系中观察到相似水平的细胞凋亡，而在罗非昔布处理后相应地较低水平。这些数据是重要的，因为它们提供了上皮和造血癌细胞系的首次直接比较，以及两种临床可用的考克斯-2抑制剂的体外抗癌作用的直接比较。
Cyclooxygenase-2 (COX-2) is an important cellular target for both therapy and/or prevention of inflammatory disorders and cancer. The advent of selective COX-2 inhibitors now allows a more precise and safer treatment approach. The screening of an array of cancer cell lines for growth inhibitory effects of COX-2-selective and -nonselective inhibitors, including celecoxib (Celebrex) and rofecoxib (Vioxx), produced two unanticipated findings. Firstly, the antiproliferative effects of celecoxib were noted to be of very similar magnitude for both hematopoietic and epithelial cancer cell lines. Most hematopoietic cell lines had no detectable COX-2 expression by reverse transcription-PCR, and none expressed COX-2 protein. In addition, COX-2-negative epithelial lines were found to have IC50s for celecoxib that were very similar to their COX-2+ counterparts. Thus, important antiproliferative effects were observed that were independent of both the cell lineage and COX-2 status. Secondly, it was also observed that COX-2 inhibitor drugs, celecoxib and rofecoxib, with similar COX-2-selectivity and clinical efficacy for inflammatory indications, differed significantly in their in vitro antiproliferative effects on cancer cell lines. IC50s of 35-65 microM were observed for celecoxib across this entire panel of cell lines. Finally, no difference in the mode or degree of cytotoxicity was apparent between cell lines, because similar levels of apoptosis were observed in COX-2+ and -negative cell lines after treatment with celecoxib, with correspondingly lower levels after rofecoxib treatment. These data are important in that they provide the first direct comparison of epithelial and hematopoietic cancer cell lines, as well as a direct comparison of the in vitro anticancer effects of the two clinically available COX-2 inhibitors.