1Department of Pediatrics, Chonbuk National University Medical School, Jeonju, Korea. 2Department of General Surgery, Chonbuk National University Medical School, Jeonju, Korea. 3Department of Research Institute of Clinical Medicine, Chonbuk National University Medical School, Jeonju, Korea.
ABSTRACT
PURPOSE: Insulin-like growth factor (IGF)-I and II are potent mitogens, postulated to exert autocrine and paracrine effects on growth regulation in human gastric cancer. In this study, we evaluated the expression of IGF-I, -II and IGFBPs in a panel of human gastric cancer cell lines. We also evaluated whether high expression of IGFBP-3 in human gastric cancer cells may increase the sensitivity to the anti-proliferative agents.
MATERIALS AND METHODS: 10 human korean gastric cancer ceIl lines and 1 Caucacian gastric adenocarcinoma cell line were used for this study. IGF and IGFBP expressions were evaluated by RT-PCR. IGFBP proteins in conditioned media were detected by Western Ligand Blot. Cell survival after treatment of anti-proliferative agents was assessed by MTT assay.
RESULTS: IGF-I and II were expressed in all gastric cancer cell lines. In addition, IGF-I and II stimulated the proliferation of gastric cancer cells. The expression of IGFBP-2 was found in all gastric cancer cell lines. IGFBP-4 was expressed in the most of cell lines. IGFBP-3, -4 and -6 were expressed in about 50% of cell lines. The growth inhibition of IGFBP-3 expressing cells by anti- proliferative agents was more significant than that of IGFBP-3 nonexpressing cells. Cell growth inhibition with treatment of these agents was accompanied by increased IGFBP-3 mRNA level.
CONCLUSION: These data confirm that IGF-I, -II, and certain IGFBPs were expressed in gastric cancer cells, and gastric cancer cells show the differential growth inhibition by anti-proliferative agents. The differential growth inhibitory effect of anti-proliferative agents is, at least in part, mediated through up-regulation of IGFBP-3 expression.
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