Mozhenok T P, Beliaeva T N, Bulychev A G, Leont'eva E A
Institute of Cytology RAS, St. Petersburg.
Tsitologiia. 2000;42(6):573-7.
Effects of polyamine (PA) synthesis inhibitors--alpha-difluoromethylornithinchloride (DFMO) and alpha-methylornithinchloride (MO)--separately or in combination with the epidermal growth factor (EGF)--on lysosome-phagosome fusion (P-LF) and F-actin content in murine peritoneal macrophages were studied using fluorescent dye Acridine orange for lysosome labelling, FITC-phalloidin for F-actin, and yeast cells as a target. DFMO and MO significantly inhibited P-LF and decreased F-actin content in murine peritoneal macrophages. A combination of DFMO and MO with EGF failed to inhibit P-LF or to decrease F-actin content in these cells. The results obtained with DFMO and MO suggested new cellular targets of their effects. These results may be extended to cancer research to provide a rationale for clinical trials using combinations of EGF with DFMO or MO.
研究了多胺(PA)合成抑制剂——α-二氟甲基鸟氨酸氯化物(DFMO)和α-甲基鸟氨酸氯化物(MO)单独使用或与表皮生长因子(EGF)联合使用对小鼠腹腔巨噬细胞溶酶体-吞噬体融合(P-LF)和F-肌动蛋白含量的影响。使用吖啶橙荧光染料标记溶酶体,用异硫氰酸荧光素-鬼笔环肽标记F-肌动蛋白,并以酵母细胞作为靶标。DFMO和MO显著抑制小鼠腹腔巨噬细胞的P-LF,并降低其F-肌动蛋白含量。DFMO和MO与EGF联合使用未能抑制这些细胞的P-LF或降低其F-肌动蛋白含量。DFMO和MO的研究结果提示了它们作用的新细胞靶点。这些结果可能扩展到癌症研究领域,为EGF与DFMO或MO联合使用的临床试验提供理论依据。