J Korean Ophthalmol Soc.  2005 May;46(5):883-895.

Inhibitory Effect of Gefitinib on the Proliferation of Lens Epithelial Cells

• Yang SJ
• Kim TH
• Lee MJ
• Shin HK
• Oh JH

Abstract

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 micro M and 10.00 micro M 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-beta2 (78% and 59%). BrdU staining demonstrated a significant decrease in cell proliferation in groups I and III exposed to more than 1.0 micro M 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-beta2 were also inhibited.

Keyword

EGF; Gefitinib; Lens epithelial cells; TGF-beta2

MeSH Terms

Blotting, Western
Bromodeoxyuridine
Carcinoma, Non-Small-Cell Lung
Cell Proliferation
Collagen Type I
Epidermal Growth Factor
Epithelial Cells*
Humans
Intercellular Signaling Peptides and Proteins
Phosphorylation
Phosphotransferases
Transforming Growth Factor beta2
Bromodeoxyuridine
Collagen Type I
Epidermal Growth Factor
Intercellular Signaling Peptides and Proteins
Phosphotransferases
Transforming Growth Factor beta2