魏红英, 郭新彪, 许珺辉, 秦宇, 王云, 邓芙蓉. 较低浓度纳米二氧化钛颗粒对细胞增殖的影响及其机制研究[J]. 环境与职业医学, 2014, 31(5): 352-357. DOI: 10.13213/j.cnki.jeom.2014.0080
引用本文: 魏红英, 郭新彪, 许珺辉, 秦宇, 王云, 邓芙蓉. 较低浓度纳米二氧化钛颗粒对细胞增殖的影响及其机制研究[J]. 环境与职业医学, 2014, 31(5): 352-357. DOI: 10.13213/j.cnki.jeom.2014.0080
WEI Hong-ying , GUO Xin-biao , XU Jun-hui , QIN Yu , WANG Yun , DENG Fu-rong . Effects and Mechanisms of Nanosized Titanium Dioxide at Lower Concentrations on Cell Proliferation[J]. Journal of Environmental and Occupational Medicine, 2014, 31(5): 352-357. DOI: 10.13213/j.cnki.jeom.2014.0080
Citation: WEI Hong-ying , GUO Xin-biao , XU Jun-hui , QIN Yu , WANG Yun , DENG Fu-rong . Effects and Mechanisms of Nanosized Titanium Dioxide at Lower Concentrations on Cell Proliferation[J]. Journal of Environmental and Occupational Medicine, 2014, 31(5): 352-357. DOI: 10.13213/j.cnki.jeom.2014.0080

较低浓度纳米二氧化钛颗粒对细胞增殖的影响及其机制研究

Effects and Mechanisms of Nanosized Titanium Dioxide at Lower Concentrations on Cell Proliferation

  • 摘要: 目的 探讨不同浓度纳米二氧化钛(nanosized titanium dioxide, Nano-TiO2)颗粒对人肺上皮细胞(A549细胞)增殖的影响及其可能机制。

    方法 采用不同粒径(5、10和40nm)和浓度(0、0.125、0.25、0.5、1、2、4、8、16mg/L)的Nano-TiO2处理A549细胞24 h,用四甲基偶氮唑盐(MTT)法和细胞计数法观察Nano-TiO2对细胞增殖的影响;用流式细胞术检测Nano-TiO2对细胞凋亡的影响;用蛋白质免疫印记法(Western Blot)测定Nano-TiO2对细胞外调节蛋白激酶(extracellular-receptor kinase, ERK)的影响。并采用ERK特异性抑制剂PD98059(20μmol/L)对细胞进行预处理30 min后,MTT法观察ERK抑制剂对低浓度Nano-TiO2(0.5 mg/L)调节细胞增殖的影响。

    结果 不同粒径的Nano-TiO2均表现出较低浓度(≤4 mg/L)促进细胞增殖,较高浓度(≥8 mg/L)抑制细胞活力的作用,而更高浓度Nano-TiO(216 mg/L)可引起细胞凋亡的发生。进一步研究发现,低浓度Nano-TiO2(0.5 mg/L)可引起细胞磷酸化ERK表达增强, ERK抑制剂PD98059可明显抑制低浓度Nano-TiO2(0.5 mg/L)的促细胞增殖作用。

    结论 低浓度Nano-TiO2可通过激活ERK促进细胞增殖,较高浓度Nano-TiO2则引发细胞凋亡发挥其抑制细胞活力的作用;不同粒径Nano-TiO2的效应之间没有明显差异。

     

    Abstract: Objective To estimate the effects of nanosized titanium dioxide (Nano-TiO2) at different concentrations on A549 human lung epithelial cell line proliferation and the potential mechanisms.

    Methods A549 cells were exposed to Nano-TiO2 with different sizes (5, 10, and 40 nm) at different concentrations (0, 0.125, 0.25, 0.5, 1, 2, 4, 8, and 16 mg/L) for 24 h. After 24 h exposure, cell proliferation was detected by tetrazolium (MTT) assay and cell number determination. Cell apoptosis and extracellular-receptor kinases (ERK) expression were determined by flow cytometry and Western Blot, respectively. MTT assay was also used to detect the effect of ERK inhibitor PD98059 (20μmol/L) on cell proliferation induced by 0.5mg/L Nano-TiO2.

    Results The Nano-TiO2 with different sizes (5, 10, and 40 nm) showed biphasic effects on the A549 cell proliferation, namely, stimulating proliferation at lower concentrations (≤ 4mg/mL), while inhibiting cell viability at higher concentrations (≥ 8mg/mL). The Nano-TiO2 at 16 mg/L induced significant increases in cell apoptosis. The results of Western Blot analysis showed that 0.5 mg/L Nano-TiO2 exposure significantly increased the expression of phosphorylated-ERK. The cell proliferation induced by 0.5 mg/L Nano-TiO2 was significantly blocked by ERK inhibitor PD98059.

    Conclusion Nano-TiO2 stimulate cell proliferation at low concentrations, while inhibite cell viability at higher concentrations. The low-concentration stimulatory effects of Nano-TiO2 could be mediated by ERK signal transduction pathway. These effects show no significant differences among Nano-TiO2 with different sizes.

     

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