Zhou Yanhong, Hu Zhaohui, Li Ningning, Jiang Renjie
Department of Clinical Laboratory, The People's Hospital of Liuzhou, Liuzhou 545006, P.R. China.
Department of Spine Surgery, The People's Hospital of Liuzhou, Liuzhou 545006, P.R. China.
Int J Mol Med. 2015 Jun;35(6):1729-33. doi: 10.3892/ijmm.2015.2159. Epub 2015 Mar 31.
As a pro-inflammatory cytokine, interleukin-32 (IL-32) is reported to play an important role in tumor development and progression. However, its effects on the invasion and motility of osteosarcoma cells remain elusive. The aim of the present study was to determine the molecular mechanisms of IL-32 in osteosarcoma cells using RT-PCR and western blot analysis. The results showed that IL-32 stimulation dose-dependently promoted the invasion and motility of osteosarcoma cells. Knockdown of endogenous IL-32 by siRNA inhibited osteosarcoma cell invasion and motility. Moreover, IL-32 induced the activation of AKT in a time-dependent manner. IL-32 stimulation was also capable of increasing the expression and secretion of matrix metalloproteinase (MMP)-13, which is involved in tumor invasion and metastasis. In addition, blockade of AKT activation suppressed IL-32-mediated invasion, motility and MMP-13 upregulation in osteosarcoma cells. Taken together, our results suggest that IL-32 stimulation promotes the invasion and motility of osteosarcoma cells, possibly via the activation of AKT and the upregulation of MMP-13 expression. Thus, IL-32 may serve as a marker for diagnosis, as well as for the treatment of osteosarcoma.
作为一种促炎细胞因子，白细胞介素-32（IL-32）据报道在肿瘤发生和发展中起重要作用。然而，其对骨肉瘤细胞侵袭和运动性的影响仍不清楚。本研究的目的是通过逆转录聚合酶链反应（RT-PCR）和蛋白质印迹分析来确定IL-32在骨肉瘤细胞中的分子机制。结果显示，IL-32刺激以剂量依赖方式促进骨肉瘤细胞的侵袭和运动性。用小干扰RNA（siRNA）敲低内源性IL-32可抑制骨肉瘤细胞的侵袭和运动性。此外，IL-32以时间依赖方式诱导AKT激活。IL-32刺激还能够增加参与肿瘤侵袭和转移的基质金属蛋白酶（MMP）-13的表达和分泌。此外，阻断AKT激活可抑制IL-32介导的骨肉瘤细胞侵袭、运动性及MMP-13上调。综上所述，我们的结果表明，IL-32刺激可能通过激活AKT和上调MMP-13表达来促进骨肉瘤细胞的侵袭和运动性。因此，IL-32可能作为骨肉瘤诊断和治疗的标志物。
