Marshall Jean-Claude, Caissie Amanda L, Cruess Stephanie R, Cools-Lartigue Jonathan, Burnier Miguel N
The Henry C, Witelson Ocular Pathology Laboratory and Registry, McGill University, 3775 University Street, Lyman Duff Building, Room 216, Montreal, Quebec H3A 2B4, Canada.
J Carcinog. 2007 Nov 27;6:17. doi: 10.1186/1477-3163-6-17.
Cyclooxygenase-2 (COX-2) expression has previously been identified in uveal melanoma although the biological role of COX-2 in this intraocular malignancy has not been elucidated. This study aimed to investigate the effect of a COX-2 inhibitor on the proliferation rate of human uveal melanoma cells, as well as its effect on the cytotoxic response of macrophages.
Human uveal melanoma cell lines were transfected to constitutively express COX-2 and the proliferative rate of these cells using two different methods, with and without the addition of Amfenac, was measured. Nitric oxide production by macrophages was measured after exposure to melanoma-conditioned medium from both groups of cells as well as with and without Amfenac, the active metabolite of Nepafenac.
Cells transfected to express COX-2 had a higher proliferation rate than those that did not. The addition of Amfenac significantly decreased the proliferation rate of all cell lines. Nitric oxide production by macrophages was inhibited by the addition of melanoma conditioned medium, the addition of Amfenac partially overcame this inhibition.
Amfenac affected both COX-2 transfected and non-transfected uveal melanoma cells in terms of their proliferation rates as well as their suppressive effects on macrophage cytotoxic activity.
环氧化酶-2(COX-2)的表达先前已在葡萄膜黑色素瘤中被发现,尽管COX-2在这种眼内恶性肿瘤中的生物学作用尚未阐明。本研究旨在探讨一种COX-2抑制剂对人葡萄膜黑色素瘤细胞增殖率的影响,以及其对巨噬细胞细胞毒性反应的影响。
将人葡萄膜黑色素瘤细胞系转染以组成性表达COX-2,并使用两种不同方法测量这些细胞在添加和不添加氨芬酸情况下的增殖率。在巨噬细胞暴露于两组细胞的黑色素瘤条件培养基以及添加和不添加奈帕芬酸的活性代谢产物氨芬酸后,测量巨噬细胞产生的一氧化氮。
转染以表达COX-2的细胞比未转染的细胞具有更高的增殖率。添加氨芬酸显著降低了所有细胞系的增殖率。添加黑色素瘤条件培养基可抑制巨噬细胞产生一氧化氮,添加氨芬酸可部分克服这种抑制作用。
氨芬酸在增殖率以及对巨噬细胞细胞毒性活性的抑制作用方面,对转染和未转染COX-2的葡萄膜黑色素瘤细胞均有影响。