霞草苷Ⅱ通过PI3K/AKT和ERK/MAPK通路下调CXCR4表达抑制DU145细胞侵袭  

Oldhamianoside Ⅱ downregulates CXCR4 expression through PI3K/AKT and ERK/MAPK pathways to inhibit DU145 cells invasion

作　　者：王燕[1] 王风玲[1] 刘静 牟艳玲[1] 李军[1] 

机构地区：[1]山东省医学科学院药物研究所山东省罕少见病重点实验室,山东济南250062 [2]济南市儿童福利院医护中心,山东济南250113

出　　处：《实用肿瘤杂志》2013年第1期71-74,共4页Journal of Practical Oncology

摘　　要：目的观察霞草苷Ⅱ(OldhamianosideⅡ)对前列腺癌DU145细胞侵袭性的影响,检测器官特异性转移相关蛋白CXC趋化因子受体4(CXC-chemokine receptor 4,CXCR4)表达的变化,并探讨其可能作用通路。方法 应用细胞划痕实验,观察霞草苷Ⅱ对DU145细胞迁移的影响;Transwell小室法,观察霞草苷Ⅱ对DU145细胞体外侵袭性的影响;免疫细胞化学方法观察DU145细胞CXCR4表达变化;Western blot检测CXCR4表达及AKT、ERK1/2的磷酸化水平。结果 细胞划痕实验显示,1 mg/L霞草苷Ⅱ处理的DU145细胞和对照组比较,细胞迁移明显减慢;体外侵袭实验结果显示,基质细胞衍生因子(stromal cell-derived factor-1,SDF-1)可明显增加DU145细胞的穿膜数量,霞草苷Ⅱ可抑制SDF-1诱导的DU145细胞侵袭;免疫细胞化学结果显示,经霞草苷Ⅱ处理后CXCR4表达下调;Western blot结果表明,霞草苷Ⅱ下调CXCR4表达,降低AKT、ERK1/2的磷酸化水平。结论 霞草苷Ⅱ通过PI3K/AKT和ERK/MAPK通路下调CXCR4表达,影响SDF-1/CXCR4反应轴,进而抑制细胞的迁移和侵袭。Objective To observe the effects of Oldhamianoside Ⅱ on invasive ability of prostatic carcinoma DU145 cells,to detect the expression of organ-specific metastasis associated protein CXC-chemokine receptor 4 （ CXCR4 ）, and to investigate the potential signal pathways. Methods The impact of Oldhamianoside II on the migration of DU145 cells was observed by scarification assay. The invasive ability was assessed with a transwell cell culture chamber. Immunocytochemistry stain was used to observe the expression of CXCR4. The expressions of CXCR4 and phosphorylated AKT, ERK1/2 were detected by Western blot assay. Results The migration of DU145 cells treated with Oldhamianoside Ⅱ was obviously decreased. Oldhamianoside U also inhibited the invasion ability of DU145 induced by SDF-1. Immunocytochemistry stain showed that Oldhamianoside II decreased the expression of CXCR4. Western blot assay showed Oldhamianoside II decreased the expression of CXCR4,and phosphorylation of AKT,ERK1/2. Conclusions Oldhamianoside Ⅱ can inhibit the migration and invasion of DU145 cells. The mechanism may be associated with the down-regulation of CXCR4 by PI3K/AKT and ERK/MAPK pathways.

关 键 词：前列腺肿瘤 霞草苷Ⅱ 治疗应用 趋化因子 CXC 趋化因子受体 信号传导 肿瘤细胞 培养的 

分 类 号：R737.25[医药卫生—肿瘤] R730.5[医药卫生—临床医学]