研究和分析CXC趋化因子受体1/2（CXCR1/2）靶向抑制剂Reparixin与紫杉醇（Ara-C）联合作用对急性髓细胞白血病细胞恶性生物学行为的影响以及对CXCR家族表达的影响，同时探讨伴随的分子机制，为AML新的分子标记和靶向治疗提供科学依据和参考。将急性髓性白血病U937细胞分别处理不同浓度的Reparixin，Ara-C或二者联合，观察细胞形态学变化，用Wright-Giemsa染色检测细胞形态学变化，使用CCK-8法检测细胞增殖，Transwell室法检测细胞侵袭能力，集落形成试验检测细胞集落形成能力，荧光染料Hoechst 33258和Annexin V/PI双染流式细胞术检测细胞凋亡，使用单胺酸酐染色检测细胞自噬，使用Western blot检测细胞凋亡、自噬和相关信号通路蛋白的表达，使用实时荧光定量聚合酶链式反应（qRT-PCR）检测CXCR家族的表达变化。Reparixin能够抑制U937细胞的增殖、侵袭、迁移和集落形成能力。与单药组相比，当U937细胞被Reparixin联合Ara-C干预时，恶性生物学行为（如增殖、侵袭和集落形成）显著降低，细胞凋亡和自噬水平显著增加（P<0.01）。经Reparixin与Ara-C干预U937细胞后，它可以上调促凋亡蛋白Bax的表达，显著下调抗凋亡蛋白Bcl-2的表达，并且水解激活Caspase-3，从而诱导细胞凋亡。Reparixin与Ara-C能够上调U937细胞中的LC3Ⅱ和Beclin-1蛋白的表达，与单药或对照组相比，细胞中LC3Ⅱ/LC3Ⅰ比例显著上调（P<0.01）。单胺酸酐染色结果显示，绿色颗粒明显增加，出现大量碎裂细胞（P<0.01）。Reparixin与Ara-C可以显著抑制PI3K、AKT和NF-κB信号分子的磷酸化水平，通过抑制PI3K/AKT/NF-κB通路的激活抑制细胞的恶性生物学行为，诱导编程性细胞死亡。Ara-C干预U937细胞对CXCR家族的表达没有影响（P>0.05）。Reparixin单药干预U937细胞可以下调CXCR1、CXCR2和CXCR4 mRNA的表达（P<0.05），而CXCR2的表达下调幅度比对照组和其他CXCR更显著（P<0.01）。Reparixin和Ara-C联合干预时，下调的CXCR1和CXCR2水平比单药组更显著（P<0.01），而CXCR4和CXCR7 mRNA的相对表达与单药组相比没有显著差异（P>0.05）。Reparixin与Ara-C联合可以协同抑制U937细胞的恶性生物学行为，如增殖、侵袭、迁移和集落形成，诱导自噬和凋亡。其机制可能涉及影响Bcl-2家族蛋白的表达，下调CXCR家族蛋白的表达，同时抑制PI3K/AKT/NF-κB信号通路。

To investigate and analyze the effect of CXC chemokine receptor 1/2 (CXCR1/2) targeting inhibitor Reparixin combined with cytarabine (Ara-C) on the malignant biological behaviors of acute myeloid leukemia cells and its effect on the expression of the CXCR family, while exploring the accompanying molecular mechanism, providing scientific basis and reference for new molecular markers and targeted therapy for AML.Acute myeloid leukemia U937 cells were treated with different concentrations of Reparixin, Ara-C alone or in combination, and the cell morphology was observed under an inverted microscope; Wright-Giemsa staining was used to detect cell morphological changes; CCK-8 method was used to detect cell proliferation; the ability of cell invasion was detected by Transwell chamber method; the ability of colony formation was detected by colony formation assay; cell apoptosis was detected by Hoechst 33258 fluorescent staining and Annexin V/PI double-staining flow cytometry; monodansylcadaverine(MDC) staining was used to detect cell autophagy; the expression of apoptosis, autophagy and related signaling pathway proteins was detected by Western blot and the expression changes of CXCR family were detected by real-time quantitative polymerase chain reaction (qRT-PCR).Reparixin could inhibit the proliferation, invasion, migration and clone formation ability of U937 cells. Compared with the single drug group, when U937 cells were intervened by Reparixin combined with Ara-C, the malignant biological behaviors such as proliferation, invasion and colony formation were significantly decreased, and the levels of apoptosis and autophagy were significantly increased (P<0.01). After Reparixin combined with Ara-C intervenes in U937 cells, it can up-regulate the expression of the pro-apoptotic protein Bax and significantly down-regulate the expression of the anti-apoptotic protein Bcl-2, and also hydrolyze and activate Caspase-3, thereby inducing cell apoptosis. Reparixin combined with Ara-C could up-regulate the expressions of LC3Ⅱ and Beclin-1 proteins in U937 cells, and the ratio of LC3Ⅱ/LC3Ⅰ in cells was significantly up-regulated compared with single drug or control group (P<0.01). MDC result showed that the green granules of vesicles increased significantly, and a large number of broken cells were seen (P<0.01). Reparixin combined with Ara-C can significantly inhibit the phosphorylation level of PI3K, AKT and NF-κB signaling molecule, inhibit the malignant biological behavior of cells by inhibiting the activation of PI3K/AKT/NF-κB pathway, and induce programmed cell death. Ara-C intervention in U937 cells had no effect on the expression of CXCR family (P>0.05). The expression of CXCR1, CXCR2, and CXCR4 mRNA could be down-regulated by Reparixin single-agent intervention in U937 cells (P<0.05), and the expression of CXCR2 was more significantly down-regulated than the control group and other CXCRs (P<0.01). When Reparixin and Ara-C intervened in combination, the down-regulated levels of CXCR1 and CXCR2 were more significant than those in the single-drug group (P<0.01), while the relative expressions of CXCR4 and CXCR7 mRNA had no significant difference compared with the single-drug group (P>0.05).Reparixin combined with Ara-C can synergistically inhibit the malignant biological behaviors of U937 cells such as proliferation, invasion, migration and clone formation, and induce autophagy and apoptosis. The mechanism may be related to affecting the proteins expression of Bcl-2 family and down-regulating the proteins expression of CXCR family, while inhibiting the PI3K/AKT/NF-κB signaling pathway.