Regolation of neuroblastoma cell growth by IGF-I

目前尚不清楚胰岛素样生长因子- i （IGF-I）如何在关键营养物质如谷氨酰胺可用性有限的情况下调节癌细胞生长。我们研究了igf - 1对谷氨酰胺缺失的人神经母细胞瘤细胞株SK-N-SH细胞生长和氨基酸运输的影响。在2 mM（对照）和100 μM谷氨酰胺浓度下，用IGF-I （50 ng/ml）处理或不加IGF-I处理后，测定细胞生长情况和^ 3h -氨基酸转运。细胞生长速率依赖于谷氨酰胺浓度。IGF-I刺激2 mM和100 μM谷氨酰胺细胞生长。在100 μM谷氨酰胺中，IGF-I通过增加载体Vmax的机制刺激谷氨酰胺转运，而在2 μM谷氨酰胺中，IGF-I对谷氨酰胺转运没有影响。在2 mM和100 μM谷氨酰胺中，IGF-I处理的细胞中^ 3h -胸苷和^ 3h -白氨酸的掺入均显著增加。在抗I型IGF受体（IGF- ir）单克隆抗体存在下，细胞增殖明显减弱，谷氨酰胺转运减少。这些数据表明，在人类神经母细胞瘤细胞系中，IGF-I/IGF-IR相互作用通过增加谷氨酰胺低水平条件下的氨基酸运输来刺激细胞生长。这种机制甚至可以在营养缺乏的肿瘤组织中维持细胞生长。

It is still unknown how insulin-like growth factor-I (IGF-I) regulates cancer cell growth in the condition of the limited availability of key nutrients, such as glutamine. We investigated the effects of IGF-I on cell growth and amino acid transport in aglutamine-deprived human neuroblastoma cell line, SK-N-SH.Cell growth was measured, and ^3H-amino acid transport was assayed after treatment with or without IGF-I (50 ng/ml) in 2 mM (control) and 100 μM glutamine concentrations. Cell growth rates were dependent on glutamine concentrations. IGF-I stimulated cell growth in both 2 mM and 100 μM glutamine. IGF-I stimulated glutamine transport in 100 μM glutamine with the mechanism of increasing carrier Vmax, but had no effect in 2 mM glutaunine There were significant increases in ^3H-thymidine and ^3H-leucine incorporation in IGF-I treated cells in both 2 mM and 100 μM glutamine. In the presence of the monoclonal antibody against the type I IGF receptor (IGF-IR), cell proliferation was significantly attenuated and glutamine transport was decreased. These data suggest that IGF-I/IGF-IR interaction stimulates cell growth by increasing amino acid transport in the condition of low glutamine levels in a human neuroblastoma cell line. This mechanism may allow to maintain cell growth even in nutrients-deprived tumor tissues.