Zhong Zhaohui, Cao Yuandong, Yang Shen, Zhang Shukun
Pharmazie. 2016 May;71(5):280-4.
The ribonucleotide reductase M2 subunit (RRM2) plays an active role in tumor progression and is frequently overexpressed in cancer. It plays a significant role in the regulation of cell invasiveness, cell migration and tumor metastasis. Elevated RRM2 expression has been reported to be associated with poor prognosis of gastric cancer. However, the molecular mechanisms of RRM2 in gastric cancer cells remain elusive. In our study, we found that RRM2 highly expressed in gastric cancer cells BGC823. RRM2 stimulation dose-dependently enhanced the invasion and migration of BGC823 cells. Furthermore, we found that the expressions of MMP-2 and MMP-9 in BGC823 cells were significantly increased after RRM2 stimulation. In addition, RRM2 time-dependently induced activation of AKT, IKBα, and NF-κB. These effects of RRM2 were prevented by AKT selective inhibitor GSK690693 as well as NF-κB selective inhibitor BAY117082. In conclusion, our findings establish a signaling role for RRM2 in gastric cancer cells and identify that the RRM2/AKT/NF-κB signaling pathway is essential for tumor invasiveness in gastric cancer cells. Thus, our data may provide knowledge for using RRM2 as a novel target for effective diagnosis and treatment of gastric cancer.
核糖核苷酸还原酶M2亚基（RRM2）在肿瘤进展中发挥积极作用，且在癌症中常过度表达。它在调节细胞侵袭、细胞迁移和肿瘤转移方面发挥着重要作用。据报道，RRM2表达升高与胃癌预后不良有关。然而，RRM2在胃癌细胞中的分子机制仍不清楚。在我们的研究中，我们发现RRM2在胃癌细胞BGC823中高表达。RRM2刺激以剂量依赖的方式增强了BGC823细胞的侵袭和迁移能力。此外，我们发现RRM2刺激后，BGC823细胞中MMP-2和MMP-9的表达显著增加。另外，RRM2以时间依赖的方式诱导AKT、IKBα和NF-κB的激活。RRM2的这些作用被AKT选择性抑制剂GSK690693以及NF-κB选择性抑制剂BAY117082所阻断。总之，我们的研究结果确立了RRM2在胃癌细胞中的信号传导作用，并确定RRM2/AKT/NF-κB信号通路对胃癌细胞的肿瘤侵袭至关重要。因此，我们的数据可能为将RRM2用作胃癌有效诊断和治疗的新靶点提供依据。
