单核细胞趋化蛋白1 在前列腺癌 进展中的调节作用

Regulatory effect of monocyte chemoattractant protein-1 on prostate cancer

摘要:

目的 探讨单核细胞趋化蛋白1（MCP-1）在前列腺癌进展中的作用。方法 采用免疫组织化学 （简称免疫组化）检测MCP-1 和血管紧张素Ⅱ 1 型受体（AT1R）在前列腺癌细胞系LNCaP，C4-2 和C4- 2AT6 中的表达。ELISA 检测Ang Ⅱ和CV11974（AT1R 阻断剂）对前列腺癌细胞系中MCP-1 生成的影响。 在C4-2AT6 细胞中，ELISA 检测Ang Ⅱ和LY294002（PI3K 抑制剂）对MCP-1 生成的影响，Western blot 检 测Ang Ⅱ和CV11974 对Akt 蛋白磷酸化水平（p-Akt）的影响，免疫组化检测TCV116（AT1R 阻断剂）对 C4-2AT6 细胞中MCP-1 和F4/80+ 表达的影响。免疫组化检测前列腺癌患者组织中MCP-1 和CD68 的表 达。结果 MCP-1 和AT1R 在前列腺癌细胞系LNCaP，C4-2 和C4-2AT6 中均表达，且在C4-2AT6 中表达 最高。在C4-2 和C4-2AT6 细胞中，Ang Ⅱ能够增加MCP-1 生成（P <0.05），而CV11974 则能够逆转Ang Ⅱ介导的MCP-1 生成增加（P <0.05）。在C4-2AT6 细胞中，LY294002 逆转了Ang Ⅱ介导的MCP-1 生成 增加（P <0.05），CV11974 能够逆转Ang Ⅱ介导的p-Akt 增加。TCV116 可降低C4-2AT6 细胞中MCP-1 和 F4/80+ 的表达（P <0.05）。前列腺癌患者组织中MCP-1 和CD68 的表达与前列腺癌的恶性程度有关，格里森 分数越高，MCP-1 和CD68 的表达越高。结论 MCP-1 可通过AT1R-PI3K/Akt 信号通路在前列腺癌恶性进 展中发挥重要作用。

Abstract:

Objective To investigate the function of monocyte chemoattractant protein-1 (MCP-1) in prostate cancer. Methods Expression levels of MCP-1 and angiotensin II type 1 receptor (AT1R) in prostate cancer cell lines LNCaP, C4-2 and C4-2AT6 were detected by the immunohistochemistry assay. Prostate cancer cell lines were treated with CV11974 (the AT1R inhibitor), LY294002 (the PI3K inhibitor) or TCV116 (the AT1R inhibitor). ELISA assay, Western blotting and immunohistochemistry were performed for measurement of several proteins including MCP- 1, phosphorylated Akt (p-Akt), CD68 and F4/80+. Results MCP-1 and AT1R were expressed in the prostate cancer cell line LNCaP, C4-2 and C4-2AT6 with the highest expression in C4-2AT6. In the C4-2 and C4-2AT6 cell line, Ang II increased the MCP-1 production (P < 0.05), which was reversed by CV11974 and LY294002 (P < 0.05). In C4- 2AT6 cell line, Ang II increased the phosphorylation of Akt (P < 0.05), which was reversed by LY294002 (P < 0.05). Treatment of TCV116 decreased the expression level of MCP-1 and CD68. Expression of MCP-1 and CD68 was positively correlated with the malignancy which was suggested by Gleason score. Conclusion MCP-1 plays an important role in the malignant progression of prostate cancer via AT1R-PI3K/Akt signaling pathway.