Antimetastatic activity of a cyclooxygenase-2 inhibitor
Antimetastatic activity of a cyclooxygenase-2 inhibitor
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DOI：
10.1038/sj.bjc.6601967
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发表时间：
2004-07-19
影响因子：
8.8
通讯作者：
Harmey, JH
中科院分区：
文献类型：
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作者：
Roche-Nagle, G;Connolly, EM;Harmey, JH
环氧合酶-2(COX-2)在乳腺癌中的表达增加，手术被证明增加了转移肿瘤的生长。我们研究了选择性COX-2抑制在实验性转移模型或切除小鼠原发乳腺肿瘤后对转移生长的影响。将5万个4T1乳腺癌细胞注入雌性BALB/c小鼠乳房脂肪垫内。当平均TD达到8+/-0.4 mm时，切除肿瘤，并将小鼠随机分为两组(每组12只)，每天接受选择性COX-2抑制剂SC-236或药物载体的腹腔注射，持续14天。或者，通过尾静脉注射50000个4T1细胞来建立实验性转移。小鼠接受选择性COX-2抑制剂SC-236或药物载体14天(每组12只)。SC-236治疗显著减少了肿瘤负担，减少了初次肿瘤切除后自发转移的数量和大小。SC-236治疗还减少了肿瘤负担，减少了实验性转移的数量和大小。免疫组织化学染色显示，COX-2抑制降低了自发和实验性转移瘤中的微血管密度，增加了细胞凋亡。这些数据清楚地表明，选择性COX-2抑制剂SC-236对原发肿瘤切除后的自发转移和实验性转移具有强大的抗转移活性。
Cyclooxygenase-2 (COX-2) expression is increased in breast cancer and surgery has been shown to increase the growth of metastatic tumours. We investigated the effect of selective COX-2 inhibition on the growth of metastases in either an experimental metastasis model or following excision of a murine primary breast tumour. 50 000 4T1 mammary carcinoma cells were injected into the mammary fat pad of female BALB/c mice. When the mean TD reached 8 +/- 0.4 mm, tumours were excised and the mice were randomised into two groups ( n = 12 per group) to receive daily intraperitoneal injections of the selective COX-2 inhibitor, SC-236 or drug vehicle for 14 days. Alternatively, experimental metastases were established by tail-vein injection of 50 000 4T1 cells. Mice received either the selective COX-2 inhibitor, SC-236 or drug vehicle for 14 days ( n = 12 per group). SC-236 treatment significantly reduced tumour burden, the number and size of spontaneous metastases following primary tumour excision. SC-236 treatment also reduced tumour burden, the number and size of experimental metastases. Immunohistochemical staining demonstrated that COX-2 inhibition reduced microvessel density and increased apoptosis within both spontaneous and experimental metastases. These data clearly demonstrate that the selective COX-2 inhibitor, SC-236, has potent antimetastatic activity against both spontaneous metastases arising following primary tumour excision and experimental metastases.