Inhibitoryeffect of gefitinib on the proliferation of lens epithelial cell

Abstract

Abstract: : Purpose: Gefitinib(Iressa^®) developed as an oral medication for non–small cell lung cancer. This study was designed to verify a possibility of the prophylactic measure for after–cataract through the observation of whether gefitinib can control the proliferation of the lens epithelial cells(LECs). Methods: The human lens epithelial cell(HLE–B3) were divided into three experiment groups, that is, group I that was exposed to gefitinib in each concentration for 3 minutes; group II that each of growth factors EGF(10ng/ml) and TGF–ß2(10ng/ml) was added; and group III that gefitinib in each concentration of 0.01, 0.10, 1.00 and 10.00 µM was exposed to EGF and TGF–ß2 10ng/ml for 3 minutes. Then, the degrees of the cell proliferation were morphologically observed with a phase–contrast microscope, and were compared through MTT assay and BrdU immunostaining. In addition, the Western blot was conducted to confirm the effects of gefitinib on ERK phosphorylation by EGF and on type I collagen generation by TGF–ß2. Results: The LECs were reduced value in the experiment group I exposed to gefitinib in concentrations of over 1.00µM, compared with the control group by MTT. The experiment group III, which was exposed to gefitinib in concentrations of over 1.00µM, exhibited a decreasing effect on the LEC proliferation by EGF, and similarly demonstrated the decrease in the administration of TGF–ß2 by MTT, BrdU. Moreover, the western blot revealed the inhibiting effects on ERK phosphorylation and type I collagen production. Conclusions: In conclusion, when the cells were exposed to gefitinib in concentrations of over 1.00µM 3 mins, it was possible to inhibit the proliferation of the LECs and to inhibit the growth factor EGF effect on the proliferation of the LECs and the TGF–ß2 effect on the production of type I collagen. If there is no toxicity in the intraocular surrounding tissue found through further toxicity experiment and in vivo experiment, the intraoperative use of gefitinib is suggested to prevent the after–cataract.

Keywords: cataract • drug toxicity/drug effects • proliferation