Williams A C, Smartt H, H-Zadeh A M, Macfarlane M, Paraskeva C, Collard T J
Cancer Research UK Colorectal Tumour Biology Research Group, Department of Cellular and Molecular Medicine, University of Bristol, School of Medical Sciences, Bristol, UK.
Cell Death Differ. 2007 Jan;14(1):137-45. doi: 10.1038/sj.cdd.4401919. Epub 2006 Apr 28.
There is growing evidence that the insulin-like growth factor-binding protein 3 (IGFBP-3) can have IGF-independent effects on cell growth. However, despite the fact that IGFBP-3 has been reported to be both antiproliferative and proapoptotic, the molecular mechanisms underlying the action of IGFBP-3 have not been elucidated. We report that although addition of IGFBP-3 (either synthetic or secreted protein) had no effect on cell survival, IGFBP-3 (100 ng/ml) significantly enhanced TNF-related apoptosis-inducing ligand (TRAIL)-induced cell death in colonic carcinoma-derived cell lines (20-30% depending on cell line), whereas it had no effect on the survival of the TRAIL-resistant adenoma-derived cells. Both addition of IGFBP-3 protein to cell cultures or enforced expression of IGFBP-3 in the HT29 carcinoma cell line inhibited nuclear factor kappa B (NF-kappaB) activation in response to the induction of apoptosis by TRAIL. We propose that IGFBP-3 is a non-toxic NF-kappaB inhibitor, which could be used as an adjuvant in the treatment of colon cancer.
越来越多的证据表明，胰岛素样生长因子结合蛋白3（IGFBP - 3）可对细胞生长产生不依赖胰岛素样生长因子（IGF）的作用。然而，尽管有报道称IGFBP - 3具有抗增殖和促凋亡作用，但其作用的分子机制尚未阐明。我们报告，虽然添加IGFBP - 3（合成蛋白或分泌蛋白）对细胞存活没有影响，但IGFBP - 3（100 ng/ml）显著增强了肿瘤坏死因子相关凋亡诱导配体（TRAIL）诱导的结肠癌细胞系中的细胞死亡（根据细胞系不同，增加20 - 30%），而对TRAIL抗性腺瘤来源的细胞存活没有影响。向细胞培养物中添加IGFBP - 3蛋白或在HT29癌细胞系中强制表达IGFBP - 3均抑制了因TRAIL诱导凋亡而引起的核因子κB（NF - κB）激活。我们提出，IGFBP - 3是一种无毒的NF - κB抑制剂，可作为结肠癌治疗的佐剂。
