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.