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-  2018 

G-CSF诱导小鼠骨髓中性粒细胞表达Bv8促进U14宫颈癌细胞成瘤及血管生成 G-CSF Induces Production of Bv8 in Murine Bone Marrow Neutrophils and Promotes Tumor Growth and Angiogenesis of U14 Murine Cervical Cancer Cell Line

Keywords: 宫颈癌,粒细胞集落刺激因子,细胞外调节蛋白激酶,中性粒细胞,前动力蛋白2

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Abstract:

目的:探讨粒细胞集落刺激因子(G-CSF)诱导小鼠骨髓中性粒细胞(PMN)生成Bv8的作用,以及其对肿瘤生长和肿瘤血管生成的作用。方法:体外实验:实时荧光定量聚合酶链式反应检测细胞内Bv8的mRNA表达,Western Blot检测PMN中细胞外调节蛋白激酶(ERK)蛋白磷酸化改变。体内实验:PMN与U14小鼠宫颈癌细胞混合成瘤,G-CSFR真核表达载体干扰G-CSF作用,抗Bv8抗体阻断Bv8作用,比较各组瘤重,免疫组织化学法检测各组肿瘤组织中的血管密度。结果:体外实验中:G-CSF刺激后,PMN中Bv8的mRNA水平明显升高(P=0.005),PMN中ERK磷酸化水平明显升高(P=0.006 7)。在G-CSF作用时加入特异性ERK抑制剂PD98059后,Bv8的mRNA水平、PMN中磷酸化ERK蛋白的水平与G-CSF刺激组相比均明显下降(P=0.008 9和0.009 8)。体内实验中:NBM-PMN抑制肿瘤生长及血管生成,TBM-PMN促进肿瘤生长及血管生成,加入G-CSFR及抗Bv8抗体后,TBM-PMN的促肿瘤生长及促血管生成作用减弱。结论:G-CSF刺激骨髓PMN生成Bv8,参与了宫颈癌肿瘤微环境改变小鼠骨髓PMN功能的过程,使其具有促进肿瘤生长及血管生成的潜能

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