Department of Neurosurgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, PR China.
Oncol Rep. 2013 May;29(5):1805-10. doi: 10.3892/or.2013.2333. Epub 2013 Mar 6.
Most human tumor cells, including glioblastoma multiforme (GBM) cells, have aberrant control of cell aging and apoptosis. Subcytotoxic concentrations of oxidative or stress‑causing agents, such as hydrogen peroxide, may induce human cell senescence. Thus, induction of tumor cells into premature senescence may provide a useful in vitro model for developing novel therapeutic strategy to combat tumors. In the present study, we assessed the molecular mechanism(s) underlying senescence in GBM cells induced by copper sulfate. Following pretreatment with subcytotoxic concentrations of copper sulfate, U87-MG tumor cells showed typical aging characteristics, including reduced cell proliferation, cell enlargement, increased level of senescence-associated β-galactosidase (SA β-gal) activity, and overexpression of several senescence-associated genes, p16, p21, transforming growth factor β-1 (TGF-β1), insulin growth factor binding protein 3 (IGFBP3) and apolipoprotein J (ApoJ). We further demonstrated that the Bmi-1 pathway was downregulated in GBM cells in parallel with the induced senescence. The present study for the first time demonstrates the ability of copper to induce GBM cell senescence by downregulating Bmi-1.
大多数人类肿瘤细胞，包括多形性胶质母细胞瘤（GBM）细胞，其细胞衰老和细胞凋亡的控制存在异常。亚细胞毒性浓度的氧化应激诱导剂，如过氧化氢，可能会诱导人类细胞衰老。因此，诱导肿瘤细胞进入过早衰老可能为开发新型治疗策略以对抗肿瘤提供有用的体外模型。在本研究中，我们评估了硫酸铜诱导 GBM 细胞衰老的分子机制。用亚细胞毒性浓度的硫酸铜预处理后，U87-MG 肿瘤细胞表现出典型的衰老特征，包括细胞增殖减少、细胞增大、衰老相关β-半乳糖苷酶（SAβ-gal）活性增加以及几个衰老相关基因（p16、p21、转化生长因子β-1（TGF-β1）、胰岛素生长因子结合蛋白 3（IGFBP3）和载脂蛋白 J（ApoJ）的过度表达。我们进一步证明，Bmi-1 通路在 GBM 细胞中与诱导的衰老平行下调。本研究首次证明了铜通过下调 Bmi-1 诱导 GBM 细胞衰老的能力。
