J Korean Ophthalmol Soc.  2003 Nov;44(11):2637-2651.

The Effect of Imatinib (Gleevec(R)) on The Proliferation of Lens Epithelial Cells and The Activities of Growth Factors

• Kim SJ
• Byun GD
• Tae JS
• Oh JH

Abstract

PURPOSE
To evaluate the effect of Imatinib which is tyrosine kinase inhibitor used for the treatment of chronic myelogenous leukemia on the proliferation of the lens epithelial cells and the activities of growth factors. METHODS: In the experimental group I, the cells were exposed to Imatinib for 3, 5 min with various concentration. In the experimental group II, the cells were cultured with PDGF, bFGF, TGF-beta2. In the experimental group III, the cells were exposed to Imatinib for 3, 5 min with the various concentration in the presence of each growth factor. The cell viability was assessed by MTT assay. And the cell proliferation were evaluated by BrdU staining. The phosphorylation of ERK (Extracellular-signal regulated kinase) and the amount of collagen type I produced by TGF-beta2 were analyzed with western blot. RESULTS: MTT assay showed that the viability of lens epithelial cells was decreased about 50% at the concentration above Imatinib 30 micro M for 5 mins exposure in group I. Both PDGF and bFFG induced significantly increased cell viability in group II. The group III that was treated with both PDGF and bFGF showed the decrease of cell viability after being exposed to Imatinib. As the concentration of Imatinib increased, BrdU incorporation of experimental group I was decreased compared with control group. It also found that The BrdU incorporation of experimental group III was also decreased compared with experimental group II. The phosphorylation of ERK 1/2 and the amount of collagen type I production was significantly decreased in addition of Imatinib 20 to 30 micro M for 3 mins exposure. CONCLUSIONS: The proliferation of lens epithelial cells could be inhibited by Imatinib. And the activities of PDGF, bFGF, TGF-beta2 were also inhibited by Imatinib.

Keyword

bFGF; Imatinib; Lens epithelial cells; PDGF; TGF-beta2

MeSH Terms

Blotting, Western
Bromodeoxyuridine
Cell Proliferation
Cell Survival
Collagen Type I
Epithelial Cells*
Intercellular Signaling Peptides and Proteins*
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Phosphorylation
Protein-Tyrosine Kinases
Transforming Growth Factor beta2
Imatinib Mesylate
Bromodeoxyuridine
Collagen Type I
Intercellular Signaling Peptides and Proteins
Protein-Tyrosine Kinases
Transforming Growth Factor beta2