白细胞介素-24通过CXC趋化因子配体12/CXC趋化因子受体4信号轴抑制肿瘤细胞转移

摘要

目的 探讨白细胞介素(IL)-24在体外实验中通过抑制CXC趋化因子配体12/CXC趋化因子受体4 (CXCL12/CXCR4)信号轴而抑制肺癌细胞迁移和侵袭.方法 以慢病毒介导IL-24基因转染H1299细胞为研究对象,研究IL-24对CXCL12/CXCR4信号轴的抑制作用.采用Western blot和Transwell细胞迁移及细胞侵袭实验评价其生物学效应.结果 IL-24在H1299-IL24细胞中的表达明显抑制了CXCR4 mRNA及蛋白的表达(P＜0.05).IL-24通过下调CXCR4的表达明显抑制了肿瘤细胞的迁移和侵袭,H1299-IL24细胞的迁移数量较对照细胞下降了约30％,侵袭能力比较对照组下降30％ ～40％,此外IL-24联合CXCR4抑制剂AMD3100使用时,表现出对肿瘤细胞迁移能力更强的抑制能力(P＜0.05).结论 IL-24通过抑制CXCL12/CXCR4信号通路,从而抑制肿瘤细胞的迁移和侵袭.此外,当IL-24联合CXCR4抑制剂使用时,表现出更强的对抗肿瘤转移的能力.%Objective To investigate whetheinterleukin-24 (IL-24) could inhibithe chemokine (C-X-motif) ligand (CXCL)-12/chemokine (C-X-motif) recepto(CXCR)-4 signaling pathway and suppreslung cancecell migration and invasion in vitro.MethodThe lung cancecell line H1299 wastably transfected with recombinanlentiviral vectorharboring open reading frame (ORF) of IL-24 and used in the presenstudy to determine the inhibitory effectof IL-24 on CXCL12/CXCR4 axis.The inhibitory effectof IL-24 on CXCL12/CXCR4 were assessed by Western blotting.Biological function wastudied using cell migration and invasion assays.ResultIL-24 expression in the H1299-IL24 cell line resulted in reduced CXCR4 expression on both mRNand protein level(P ＜ 0.05).Functional studieshowed thaIL-24 inhibited tumocell migration (30％ decrease) and invasion (30％-40％ decrease, P ＜0.05).Finally, IL-24, when combined with CXCR4 inhibito(AMD3100), demonstrated enhanced inhibitory activity on tumocell migration (P ＜ 0.05).Conclusion IL-24 interferewith the CXCL12/CXCR4 signaling pathway and inhibitlung tumocell migration and invasion.Additionally,IL-24, when combined with CXCR4 inhibitor, exhibited enhanced anti-metastatiactivity.