title: Insulin-like growth factor binding protein-3 enhances etoposide-induced cell growth inhibition by suppressing the NF-κB activity in gastric cancer cells.
abstract: Nuclear factor-kappaB (NF-κB) is a transcription factor that is activated in various neoplasms, including gastric cancer. Insulin-like growth factor binding protein-3 (IGFBP-3) is a potent tumor suppressor and is significantly suppressed in a variety of cancers. Although IGFBP-3 has been reported to have antiproliferative and proapoptotic effects, the precise mechanisms underlying the action of IGFBP-3 have not been elucidated. In this study, we found an inverse correlation between NF-κB activity and IGFBP-3 expression in patients with gastric cancer. Overexpression of IGFBP-3 resulted in significant inhibition of total and phosphorylated p65 NF-κB and IκB proteins in gastric cancer cells. IGFBP-3 further inhibited the expression of NF-κB-regulated cell adhesion molecules, ICAM-1 and VCAM-1. Finally, the growth inhibition induced by etoposide was significantly enhanced by IGFBP-3 overexpression along with concomitant suppression of NF-κB activity. These findings indicate that IGFBP-3 enhances etoposide-induced cell growth inhibition by blocking the NF-κB signaling pathway in gastric cancer cells. Furthermore, our data suggest that IGFBP-3 could be used as an adjuvant in the treatment of gastric cancer.
authors: Department of Pediatrics, Chonbuk National University Medical School, Chonbuk National University Hospital, 634-18 Keumam-dong, Jeonju, 561-712, Korea.
authors: Min Sun
authors: MS
authors: Kim
authors: Dae-Yeol
authors: DY
authors: Lee
mesh_terms: D015815:Cell Adhesion Molecules / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D005047:Etoposide / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D015398:Signal Transduction; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*
chemical_list: D015815:Cell Adhesion Molecules; D018972:Insulin-Like Growth Factor Binding Protein 3; D016328:NF-kappa B; D005047:Etoposide