Liu X H, Yao S, Kirschenbaum A, Levine A C
Department of Urology, Mount Sinai Medical Center, New York, New York 10029, USA.
Cancer Res. 1998 Oct 1;58(19):4245-9.
Cyclooxygenase (COX)-2, an inducible enzyme that catalyzes the formation of prostaglandins and other eicosanoids from arachidonic acid, is constitutively expressed in LNCaP human prostate cancer cell line. To evaluate the potential role of COX-2 in prostate cancer, LNCaP cells were treated with NS398, a selective COX-2 inhibitor, and the effects on cell viability and apoptosis were determined. NS398 treatment induced apoptosis in LNCaP cells in a time- and dose-dependent fashion. Treatment with 100 microM NS398 caused a down-regulation in bcl-2 protein expression, followed by chromatin condensation, chromosomal DNA fragmentation, and changes in nuclear morphology detected by 4,6-diamidino-2-phenylindole staining, DNA fragmentation assay, and terminal deoxynucleotidyl transferase-mediated UTP-biotin nick end-labeling assay. In contrast, NS398 treatment had no effect on either cell viability or nuclear function and morphology in human fetal prostate fibroblasts. These results demonstrate that NS398 induces apoptosis in LNCaP cells but not in human fetal prostate fibroblasts, and that this induction is associated with a decreased level of bcl-2 protein.
环氧化酶（COX）-2是一种诱导性酶，可催化花生四烯酸生成前列腺素和其他类二十烷酸，在LNCaP人前列腺癌细胞系中组成性表达。为评估COX-2在前列腺癌中的潜在作用，用选择性COX-2抑制剂NS398处理LNCaP细胞，并测定其对细胞活力和凋亡的影响。NS398处理以时间和剂量依赖性方式诱导LNCaP细胞凋亡。用100 microM NS398处理导致bcl-2蛋白表达下调，随后出现染色质浓缩、染色体DNA片段化以及通过4,6-二脒基-2-苯基吲哚染色、DNA片段化分析和末端脱氧核苷酸转移酶介导的UTP-生物素缺口末端标记分析检测到的核形态变化。相反，NS398处理对人胎儿前列腺成纤维细胞的细胞活力或核功能及形态均无影响。这些结果表明，NS398诱导LNCaP细胞凋亡，但不诱导人胎儿前列腺成纤维细胞凋亡，且这种诱导与bcl-2蛋白水平降低有关。
