Qu Hu, Zou Zihao, Pan Zhaojun, Zhang Tianwei, Deng Nan, Chen Guoxi, Wang Zhongyang
Department of Urology, the Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou 510655, PR China.
Department of Urology, the Third Affiliated Hospital of Guangzhou Medical University, Guangzhou 510150, PR China.
Int Immunopharmacol. 2016 Nov;40:203-210. doi: 10.1016/j.intimp.2016.08.017. Epub 2016 Sep 7.
IL-7, acting via IL-7 receptor (IL-7R), plays an important role in tumor progression. Elevated IL-7 expression has been reported to be observed in prostate cancer tissues and closely associated with poor prognosis. However, the biological functions of IL-7 and its receptor in prostate cancer cell invasiveness remain unclear. In our study, we found that the expressions of IL-7 and IL-7R were both upregulated in prostate cancer cells. IL-7 dose-dependently promoted the invasion and migration of prostate cancer cells, whereas knockdown of IL-7R attenuated the effect of IL-7. Further, IL-7/IL-7R axis induced the activation of AKT and NF-κB, whereas blocking of AKT suppressed IL-7-mediated NF-κB activity. Moreover, IL-7/IL-7R axis increased MMP-3 and MMP-7 expression of prostate cancer cells, whereas inhibition of NF-κB as well as MMPs activity suppressed IL-7-mediated cell invasion and migration. Together, these data identify IL-7/IL-7R axis to be involved in prostate cancer cell invasion and migration, probably via activating AKT/NF-κB pathway and upregulating MMP-3 and MMP-7 expression. Therefore, blocking IL-7/IL-7R axis may provide a potential therapeutic strategy to treat prostate cancer.
白细胞介素-7(IL-7)通过白细胞介素-7受体(IL-7R)发挥作用,在肿瘤进展中起重要作用。据报道,在前列腺癌组织中观察到IL-7表达升高,且与预后不良密切相关。然而,IL-7及其受体在前列腺癌细胞侵袭性中的生物学功能仍不清楚。在我们的研究中,我们发现前列腺癌细胞中IL-7和IL-7R的表达均上调。IL-7以剂量依赖的方式促进前列腺癌细胞的侵袭和迁移,而敲低IL-7R则减弱了IL-7的作用。此外,IL-7/IL-7R轴诱导AKT和NF-κB的激活,而阻断AKT则抑制IL-7介导的NF-κB活性。此外,IL-7/IL-7R轴增加前列腺癌细胞中基质金属蛋白酶-3(MMP-3)和基质金属蛋白酶-7(MMP-7)的表达,而抑制NF-κB以及MMPs的活性则抑制IL-7介导的细胞侵袭和迁移。总之,这些数据表明IL-7/IL-7R轴可能通过激活AKT/NF-κB途径并上调MMP-3和MMP-7的表达参与前列腺癌细胞的侵袭和迁移。因此,阻断IL-7/IL-7R轴可能为治疗前列腺癌提供一种潜在的治疗策略。