Department of Biology, Hong Kong Baptist University, PR China.
Cancer Lett. 2013 Jul 10;335(1):81-92. doi: 10.1016/j.canlet.2013.01.052. Epub 2013 Feb 8.
Macrophage migration inhibitory factor (MIF) and CXCL8 (also named IL-8) are strongly expressed in the tissues of nasopharyngeal carcinoma (NPC). However, their role in the growth of NPC has not been fully examined. This study aims to evaluate the functions of MIF and CXCL8 on the growth of NPC tumor spheres. The elevated expression of CXCL8 in tumor over normal tissues was confirmed in 37 pairs of biopsies from NPC patients. In the in vitro study, all the poorly differentiated NPC cell lines, including the EBV-positive C666-1, and the EBV-negative CNE-1, CNE-2, SUNE-1, HNE-1 and HONE-1 cells, were found to express CXCL8 and MIF. Therefore, the EBV-positive C666-1 cell was selected to examine for the role of MIF and CXCL8 in the growth of the NPC tumor spheres. Functional study showed that the growth of C666-1 tumor spheres, under the nutrient poor or growth factor supplemented culture conditions, could be inhibited by the CXCL8 specific peptide inhibitor. The growth of the tumor spheres could also be reduced by the CXCR2 specific inhibitor SB225002 or the PI3K/AKT inhibitor LY294002, indicating that the endogenously produced CXCL8 plays an autocrine role in the growth of the tumor spheres. Further mechanistic studies revealed that the gene expression of CXCL8 could be reduced by the MIF specific small interfering RNA (siRNA) or NF-κB inhibitor parthenolide, and the growth of tumor spheres was also reduced after MIF siRNA transfection. Taken together, the present study highlights the role of MIF/CXCL8/CXCR2 axis in the growth of NPC tumor spheres. Chemotherapeutic interference of this signaling pathway may help to control the growth of the NPC tumor.
巨噬细胞移动抑制因子 (MIF) 和 CXCL8（也称为 IL-8）在鼻咽癌 (NPC) 组织中强烈表达。然而，它们在 NPC 生长中的作用尚未被充分研究。本研究旨在评估 MIF 和 CXCL8 对 NPC 肿瘤球体生长的功能。在 37 对 NPC 患者活检组织中证实，肿瘤中 CXCL8 的表达高于正常组织。在体外研究中，所有低分化 NPC 细胞系，包括 EBV 阳性的 C666-1 和 EBV 阴性的 CNE-1、CNE-2、SUNE-1、HNE-1 和 HONE-1 细胞，均表达 CXCL8 和 MIF。因此，选择 EBV 阳性的 C666-1 细胞来研究 MIF 和 CXCL8 在 NPC 肿瘤球体生长中的作用。功能研究表明，在营养缺乏或生长因子补充的培养条件下，C666-1 肿瘤球体的生长可以被 CXCL8 特异性肽抑制剂抑制。肿瘤球体的生长也可以被 CXCR2 特异性抑制剂 SB225002 或 PI3K/AKT 抑制剂 LY294002 降低，表明内源性产生的 CXCL8 在肿瘤球体的生长中发挥自分泌作用。进一步的机制研究表明，CXCL8 的基因表达可以被 MIF 特异性小干扰 RNA (siRNA) 或 NF-κB 抑制剂白头翁素降低，并且在 MIF siRNA 转染后肿瘤球体的生长也降低。综上所述，本研究强调了 MIF/CXCL8/CXCR2 轴在 NPC 肿瘤球体生长中的作用。该信号通路的化疗干预可能有助于控制 NPC 肿瘤的生长。
