Growth-inhibitory and differentiation-inducing activity of dimethylformamide in cultured human malignant glioma cells

OBJECTIVE: To determine the growth-inhibitory and differentiation-inducing activity of dimethylformamide (DMF) on a human glioma cell line (SHG-44). DMF is a type of polar solvent and a potent differentiation-inducing agent in many kinds of human solid tumors, yet its effect on human glioma remains unclear. METHODS: The effects of DMF on cell proliferation using 3-(4,5-dimethyl thiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay, cell cycle distribution (with flow cytometry), colony-forming efficiency in double-layer soft agar, tumorigenicity in athymic nude mice, morphological changes, and glial fibrillary acidic protein expression were studied. RESULTS: At dose ranges of 0.25, 0.5, 0.75, and 1.0%, DMF caused a dose-dependent proliferation inhibitory effect in monolayers and a marked dose-dependent suppression of colony-forming efficiency in double-layer soft agar with a complete loss of colony-forming ability in cells exposed to 0.75 and 1.0% DMF. Accumulation of cells in G0/G1 phases was observed in DMF-treated (0.5 and 1.0%) cells, also in a dose-dependent manner. SHG-44 cells exposed to DMF (0.5 and 1.0%) for 15 days changed morphologically from small spindle-shaped to large polygonal and flattened stellate cells with multiple slender processes. These cells were still tumorigenic in athymic nude mice, but the growth of xenografts was remarkably reduced, especially in the 1.0% DMF-treated group. The expression of glial fibrillary acidic protein was notably increased by DMF (0.5 and 1.0%). Washout experiments revealed that the effects of DMF on cell proliferation and cell cycle distribution were reversible. CONCLUSION: Our results suggest that DMF drove the SHG-44 cells to a more mature phenotype with inhibited growth.     

利物浦博物馆

由丹麦事务所3XN设计的利物浦博物馆于2011年7月19日正式建成开幕。它不仅向我们述说了作为世界上最重要的港口的作用,或者披头士现象的文化影响,而且将成为世界各地参观者的聚焦点。正如建筑师Kim Herforth Nielsen所说,设计本身超越了建筑或是博物馆的功能。