吞噬细胞运动蛋白1在IL-8诱导的乳腺癌细胞的侵袭和转移中发挥重要作用

摘要

Aim To explore the relationship between IL-8 and ELMO1 in breast carcinoma and the mecha-nisms of IL-8 induced invasion and metastasis. Meth-ods Under the IL-8 stimulation, chemotaxis assay was examined to detect the chemotaxis ability of breast cancer cell line MDA-MB-231 and MCF-7 . ELMO1 protein levels in breast cancer cell lines were detected using Western blot. MDA-MB-231 cells were transfect-ed with small RNA interference plasmids in order to downregulate ELMO1 expression, and overexpression plasmids were used to upregulate the expression of EL-MO1 in MCF-7 cells. Matrigel invasion assay and chemotaxis assay were used to detect the in vitro inva-sion and chemotaxis ability of breast cancer cells with IL-8 stimulation. Results IL-8 induced chemotaxis of the different breast cancer cell lines in a dose-depend-ent manner. After transient transfection, Western blot results showed that ELMO 1 protein levels observably decreased in SiELMO1/MDA-MB-231 cells compared with Scr/MDA-MB-231 cells, while the expression of ELMO1 protein levels significantly increased in MCF-7/ELMO1 cells compared with the MCF-7/Con cells;with IL-8 stimulation, SiELMO1/MDA-MB-231 cells showed significantly decreased chemotaxis ability com-pared with Scr/MDA-MB-231 cells. MCF-7/ELMO1 cells showed significantly increased chemotaxis ability compared with MCF-7/Con cells; the invasion assay showed under the stimulation of IL-8 , and the invasion ability was significantly reduced in SiELMO1/MDA-MB-231 cells compared with Scr/MDA-MB-231 cells ( P<0. 05 ) . The invasion ability was significantly en-hanced in MCF-7/ELMO1 cells compared with MCF-7 cells( P<0. 05 ) . Conclusion IL-8 promotes the in-vasion and migration of breast cancer cells MDA-MB-231 and MCF-7 , and ELMO1 plays an important role in IL-8 induced chemotaxis and invasion.%目的：探讨吞噬细胞运动蛋白1( engulfment and cell motility 1, ELMO1)在IL-8诱导的乳腺癌细胞侵袭和转移过程中的作用。方法采用趋化运动实验检测不同浓度IL-8刺激下乳腺癌细胞的趋化运动能力；采用Western blot检测乳腺癌细胞中ELMO1的表达情况；利用小RNA干扰技术,瞬时转染乳腺癌细胞MDA-MB-231,用过表达质粒上调乳腺癌细胞MCF-7中ELMO1的表达；应用趋化运动实验和Tran-swell侵袭实验检测各组转染细胞的趋化和侵袭能力。结果趋化运动实验结果显示,在 IL-8刺激下,乳腺癌细胞MDA-MB-231和MCF-7的运动能力明显增强,具有剂量依赖性；Western blot结果显示ELMO1在siELMO1/MDA-MB-231细胞中的表达明显降低,而在MCF-7/ELMO1细胞中的表达明显增高；趋化运动实验结果显示在IL-8刺激下,SiELMO1/MDA-MB-231细胞组的趋化运动能力明显降低, MCF-7/EL-MO1细胞组的趋化运动能力明显增强；Transwell侵袭实验结果显示在 IL-8刺激下,敲除 ELMO1明显降低 MDA-MB-231细胞的侵袭能力,过表达 ELMO1明显增强MCF-7细胞的侵袭能力。结论 IL-8能促进MDA-MB-231和MCF-7细胞的趋化运动和侵袭能力,而ELMO1在IL-8诱导的乳腺癌细胞趋化和侵袭作用中发挥重要作用。