Wang L, Zheng W, Zhang S, Chen X, Hornung D
Department of Gynaecology, Second Affiliated Hospital, Medical College, Zhejiang University, Hangzhou, China.
J Int Med Res. 2006 May-Jun;34(3):284-90. doi: 10.1177/147323000603400307.
Monocyte chemotactic protein-1 (MCP-1) is an important determinant of macrophage infiltration in tumours. This study investigated the effect of tamoxifen and the gonadotrophin-releasing hormone agonist buserelin on MCP-1 in the human endometrial cancer cell line EFE-184. Reverse transcription polymerase chain reaction and Western blot analysis were used to determine MCP-1 mRNA and protein expression, respectively. Immunoreactive MCP-1 in the cell culture media was quantified by enzyme-linked immunosorbent assay. Tamoxifen inhibited MCP-1 mRNA and protein expression in endometrial cancer cells and inhibited MCP-1 secretion in a time- and dose-dependent manner at concentrations of 10(-7) to 10(-5) M. Buserelin had no significant effect on MCP-1 mRNA and protein expression. These results suggest that tamoxifen directly inhibits the expression of MCP-1 in this cell line by blocking the MCP-1 signalling pathways. These findings may contribute to the understanding of the mechanisms underlying the different effects of tamoxifen and gonadotrophin-releasing hormone agonists in the treatment of endometrial cancer.
单核细胞趋化蛋白-1(MCP-1)是肿瘤中巨噬细胞浸润的重要决定因素。本研究调查了他莫昔芬和促性腺激素释放激素激动剂布舍瑞林对人子宫内膜癌细胞系EFE-184中MCP-1的影响。分别采用逆转录聚合酶链反应和蛋白质免疫印迹分析来测定MCP-1 mRNA和蛋白表达。通过酶联免疫吸附测定法对细胞培养基中的免疫反应性MCP-1进行定量。他莫昔芬在浓度为10^(-7)至10^(-5) M时,以时间和剂量依赖性方式抑制子宫内膜癌细胞中MCP-1 mRNA和蛋白表达,并抑制MCP-1分泌。布舍瑞林对MCP-1 mRNA和蛋白表达无显著影响。这些结果表明,他莫昔芬通过阻断MCP-1信号通路直接抑制该细胞系中MCP-1的表达。这些发现可能有助于理解他莫昔芬和促性腺激素释放激素激动剂在治疗子宫内膜癌中不同作用的潜在机制。