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

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Ⅱ1型受体(AT1R)在前列腺癌细胞系LNCa P,C4-2和C4-2AT6中的表达。ELISA检测AngⅡ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AngⅡ和LY294002(PI3K抑制剂)对MCP-1生成的影响,Western blot检测AngⅡ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,AngⅡ能够增加MCP-1生成(P <0.05),而CV11974则能够逆转AngⅡ介导的MCP-1生成增加(P <0.05)。在C4-2AT6细胞中,LY294002逆转了AngⅡ介导的MCP-1生成增加(P <0.05),CV11974能够逆转AngⅡ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。

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.