基因CXCL8促进结直肠癌进展的机制研究

The mechanism of CXCL8 promoting colorectal cancer progression

目的:探究白细胞介素8(interleukin-8,IL-8,又称CXCL8)在结直肠癌中的表达水平和作用机制。方法:生物信息学分析癌细胞系百科全书(Cancer Cell Line Encyclopedia,CCLE)、癌症基因组图谱(The Cancer Genome Atlas,TCGA)数据库中CXCL8的泛癌表达及在结直肠癌中的表达。体外构建结直肠癌细胞SW480和HCT116的CXCL8敲低模型,通过检测肿瘤细胞的增殖能力,并用Western Blot验证信号通路。生信分析CXCL8对肿瘤免疫微环境的影响,并通过结直肠癌细胞与巨噬细胞体外共培养验证。结果:CXCL8在结直肠癌组织相比癌旁组织显著高表达(P<0.05)。体外实验证明,CXCL8能通过磷酸肌醇3-激酶(phosphatidylinositol 3-kinase,PI3K)信号通路调控肿瘤细胞的增殖,并能通过旁分泌的形式维持M2样巨噬细胞标记基因的表达。结论:CXCL8在结直肠癌中高表达,通过PI3K/Akt/mTOR信号通路促进肿瘤细胞的增殖,对维持M2样巨噬细胞的肿瘤微环境有着重要作用。

Objective:To explore the expression level and mechanism of interleukin-8(IL-8,also named CXCL8)in colorectal cancer.Methods:The Cancer Cell Line Encyclopedia(CCLE)was used to analyze the expression of CXCL8 in cancer cell lines and The Cancer Genome Atlas(TCGA)was analyze the expression of CXCL8 in colorectal cancer.CXCL8 in the SW480 and HCT116 cell lines were knockdown in vitro.The proliferation ability of tumor cells was detected and the signaling pathway was verified by Western Blot.The effect of CXCL8 on tumor immune microenvironment was analyzed by bioinformatics and verified by co-culture of colorectal cancer cells and macrophages in vitro.Results:CXCL8 expression levels in colorectal cancer tissues were significantly increased compared with the paracancerous normal tissues.CXCL8 regulated cell proliferation via the phosphatidylinositol 3-kinase(PI3K)signalling pathway in vitro and supports the maintenance of the M2-like phenotype.Conclusion:CXCL8 is highly expressed in colorectal cancer and promotes tumor cell proliferation through the PI3K/Akt/mTOR signaling pathway.CXCL8 plays an important role in the tumor microenviroment by maintaining M2-like macrophages through paracrine.