Inhibition of cyclooxygenase-2 suppresses invasiveness of oral squamous cell carcinoma cell lines via down-regulation of matrix metalloproteinase-2 and CD44
Inhibition of cyclooxygenase-2 suppresses invasiveness of oral squamous cell carcinoma cell lines via down-regulation of matrix metalloproteinase-2 and CD44
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DOI：
10.1007/s10585-005-1190-x
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发表时间：
2004-01-01
影响因子：
4
通讯作者：
Nagumo, M
中科院分区：
文献类型：
--
作者：
Kinugasa, Y;Hatori, M;Nagumo, M
已知肿瘤中环氧合酶-2（考克斯-2）的表达与增强的血管生成、抑制宿主免疫和肿瘤侵袭相关。本研究以人口腔鳞状细胞癌（OSCC）细胞株NA和HSC-4为研究对象，观察考克斯-2选择性抑制剂NS-398和考克斯-2反义寡核苷酸（考克斯-2 AS）对OSCC细胞侵袭能力的影响。基质胶侵袭实验显示NS-398或考克斯-2 AS均能抑制NA和HSC-4的侵袭能力。这些试剂下调基质金属蛋白酶-2（MMP-2）向培养上清的分泌以及MMP-2 mRNA和蛋白的表达。膜1型基质金属蛋白酶（MT 1-MMP），proMMP-2的激活剂，也下调了这些试剂的治疗。此外，通过用NS-398或考克斯-2 AS处理，这些细胞表面上的CD 44表达降低。此外，MMP-2反义寡核苷酸降低了两种OSCC细胞系表面CD 44的表达。这些结果表明，NS-398和考克斯-2 AS通过下调MMP-2和CD 44抑制OSCC细胞的侵袭能力。因此，对考克斯-2的遗传或药理学抑制可能是治疗OSCC患者的有益策略。
Expression of cyclooxygenase-2 (COX-2) in tumors is known to be associated with enhanced angiogenesis, suppression of host immunity, and tumor invasion. In the present study, human oral squamous cell carcinoma (OSCC) cell lines NA and HSC-4 were used to evaluate the effects of NS-398, a selective inhibitor of COX-2, and COX-2 antisense oligonucleotide (COX-2 AS) on the invasion activity of OSCC cells. Matrigel invasion assay revealed that the invasiveness of NA and HSC-4 was suppressed by treatment with either NS-398 or COX-2 AS. These reagents down-regulated the secretion of matrix metalloproteinase-2 (MMP-2) to culture supernatant as well as the expression of MMP-2 mRNA and protein. Membrane-type 1 matrix metalloproteinase (MT1-MMP), an activator of proMMP-2, was also down-regulated by treatment with these reagents. Furthermore, expression of CD44 on the surface of these cells was reduced by treatment with either NS-398 or COX-2 AS. In addition, MMP-2 antisense oligonucleotides reduced the expression of CD44 on the surface of both OSCC cell lines. These findings suggest that NS-398 and COX-2 AS suppress the invasiveness of OSCC cells via down-regulation of MMP-2 and CD44. Genetic or pharmacological inhibition of COX-2 may therefore be a beneficial strategy in the treatment of OSCC patients.