Inhibition of cyclooxygenase-2 decreases breast cancer cell motility, invasion and matrix metalloproteinase expression.
Inhibition of cyclooxygenase-2 decreases breast cancer cell motility, invasion and matrix metalloproteinase expression.
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DOI：
10.1186/1471-2407-6-181
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发表时间：
2006-07-10
期刊：
影响因子：
3.8
通讯作者：
Sanford GL
中科院分区：
文献类型：
--
作者：
Larkins TL;Nowell M;Singh S;Sanford GL
环氧合酶(COX)是催化前列腺素形成的限速酶。COX-2的诱导型亚型在侵袭性转移性乳腺癌中高表达，可能在肿瘤的发展(即生长和转移)中起关键作用。然而，COX-2促进肿瘤转移的确切机制(S)尚不清楚。众所周知，COX-2作用的直接结果之一是增加前列腺素的产生，特别是前列腺素E2(PGE2)。在这里，我们将COX-2活性的抑制与乳腺癌细胞增殖、迁移、侵袭和基质金属蛋白酶(MMPs)表达的减少联系起来。用选择性COX-2抑制剂NS-398和尼氟米酸(NA)处理乳腺癌细胞(Hs578T、MDA-MB-231和MCF-7)。红素B染色和血细胞计数法检测细胞增殖情况。用迁移和侵袭小室系统测量细胞的迁移和侵袭。用酶免疫分析(分泌型蛋白)和实时定量聚合酶链式反应(MRNA)检测基质金属蛋白酶的表达。结果表明，在低浓度(1μM或更低)NA或NS-398存在下，Hs578T和mda-MB-231乳腺癌细胞株的增殖、迁移和侵袭能力均下降。我们还报道了NS-398对Hs578T细胞MMPmRNA和蛋白表达的抑制作用；100μM NS-398可抑制Hs578T细胞MMPmRNA和蛋白的表达。PGE2可完全逆转NS-398对MMPmRNA表达的抑制作用。我们的数据表明，COX-2依赖的活性是乳腺癌细胞运动和侵袭的细胞和分子机制的必要组成部分。COX-2活性也调节MMPs的表达，这可能是COX-2促进细胞侵袭和迁移的分子机制之一。研究表明，COX-2有助于确定和定义促进乳腺癌进展到转移的转移信号通路。
Cyclooxygenase (COX) is the rate-limiting enzyme that catalyzes the formation of prostaglandins. The inducible isoform of COX (COX-2) is highly expressed in aggressive metastatic breast cancers and may play a critical role in cancer progression (i.e. growth and metastasis). However, the exact mechanism(s) for COX-2-enhanced metastasis has yet to be clearly defined. It is well established that one of the direct results of COX-2 action is increased prostaglandin production, especially prostaglandin E2 (PGE2). Here, we correlate the inhibition of COX-2 activity with decreased breast cancer cell proliferation, migration, invasion and matrix metalloproteinase (MMP) expression. Breast cancer cells (Hs578T, MDA-MB-231 and MCF-7) were treated with selective COX-2 inhibitors (NS-398 and Niflumic acid, NA). Cell proliferation was measured by staining with erythrosin B and counting the viable cells using a hemacytometer. Cell migration and invasion were measured using migration and invasion chamber systems. MMP expression was determined by enzyme immunoassay (secreted protein) and real-time quantitative polymerase chain reaction (mRNA). Our results show that there is a decline in proliferation, migration and invasion by the Hs578T and MDA-MB-231 breast cancer cell lines in the presence of either low concentrations (1 μM or lower) NA or NS-398. We also report that MMP mRNA and protein expression by Hs578T cells is inhibited by NS-398; there was a 50% decrease by 100 μM NS-398. PGE2 completely reversed the inhibitory effect of NS-398 on MMP mRNA expression. Our data suggests that COX-2-dependent activity is a necessary component for cellular and molecular mechanisms of breast cancer cell motility and invasion. COX-2 activity also modulates the expression of MMPs, which may be a part of the molecular mechanism by which COX-2 promotes cell invasion and migration. The studies suggest that COX-2 assists in determining and defining the metastatic signaling pathways that promote the breast cancer progression to metastasis.
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影响因子：
5.3
作者：
Han, SW;Roman, J
通讯作者：
Roman, J
影响因子：
2.2
作者：
Mohseni, H;Zaslau, S;Kandzari, S
通讯作者：
Kandzari, S
DOI：
10.1111/j.1349-7006.1996.tb00266.x
发表时间：
1996-06-01
期刊：
JAPANESE JOURNAL OF CANCER RESEARCH
影响因子：
--
作者：
Iwata, H;Kobayashi, S;Okada, Y
通讯作者：
Okada, Y
DOI：
10.1046/j.1524-4741.2000.99025.x
发表时间：
2000-03-01
期刊：
The breast journal
影响因子：
--
作者：
Guyton, Daniel P.;Evans, Douglas M.;Sloan-Stakleff, Kimberly D.
通讯作者：
Sloan-Stakleff, Kimberly D.
环氧酶-2抑制剂Celecoxib在人乳腺癌细胞中的生长抑制作用的基础机制。
影响因子：
7.4
作者：
Basu, GD;Pathangey, LB;Tinder, TL;Gendler, SJ;Mukherjee, P
通讯作者：
Mukherjee, P