게피티니브의 수정체상피세포에 대한 증식억제 효과

Inhibitory Effect of Gefitinib on the Proliferation of Lens Epithelial Cells

Purpose: To evaluate the effect of Gefitinib used for the treatment of non-small cell lung cancer on the proliferation of the lens epithelial cells and the activities of growth factors. Methods: The cell samples were divided into a control group cultured in DMEM and three experimental groups. Group I was exposed to Gefitinib for 3 minutes; group II was exposed to growth factors; and for group III growth factors were added to each concentration of Gefitinib. MMT assays, BrdU staining and morphologically observations with a phase-contrast microscope were used to verify the degrees of cell proliferation. Western blot analysis was conducted to confirm the effects of Gefitinib on extracellular signal-regulated kinase phosphorylation and on type I collagen production. Results: Lens epithelial cell proliferation in experimental group I was reduced to 76% and 56% for 1.00 μM and 10.00 μM of Gefitinib, respectively. Experimental group II showed a 140% increase in cell proliferation with EGF treatment. Experimental group III exhibited decreased lens epithelial cell proliferation with both EGF (86% and 66%), and TGF-β2 (78% and 59%). BrdU staining demonstrated a significant decrease in cell proliferation in groups I and III exposed to more than 1.0 μM Gefitinib, while group II showed an increase compared to the control group. Moreover, Western blot analysis revealed inhibiting effects on ERK phosphorylation and type I collagen production. Conclusions: In the culture of human lens epithelial cells, Gefitinib inhibited cell proliferation when used at a concentration above 1.00 (M for 3 minutes. Furthermore, the effects of EGF and TGF-β2 were also inhibited.