The mechanism of the inhibitory action of lipopolysaccharide on anti-cancer drug-induced cell injury

以小鼠RAW 264.7巨噬细胞为模型，研究了脂多糖对阿霉素诱导的细胞死亡的影响。10 ng/ml的内毒素可抑制DXB诱导的细胞死亡，其抑制作用大致依赖于内毒素的浓度。内毒素处理后1h也可阻止DXB诱导的细胞死亡。脂多糖抑制地塞米松诱导的RAW 264.7细胞DNA片段化和半胱氨酸天冬氨酸蛋白酶3的激活，提示其对地塞米松诱导的细胞凋亡有保护作用。单细胞凝胶电泳法检测，脂多糖对DXB诱导的DNA损伤没有明显的抑制作用。脂多糖明显抑制地塞米松处理的RAW 264.7细胞中P53的稳定和核转位。脂多糖和P53抑制剂可阻断DXB诱导的细胞凋亡。因此，P53基因在地塞米松诱导RAW 264.7细胞凋亡中可能起着重要作用。

The effect of lipopolysaccharide (LPS) on doxorubicin (DXB)-induced cell death was studied by using mouse RAW 264.7 macrophage cells. Pretreatment with LPS at 10ng/ml prevented DXB-induced cell death and the inhibition was roughly dependent on the concentration of LPS. The 1 h post-treatment of LPS also prevented DXB-induced cell death. LPS inhibited DNA fragmentation and caspase 3 activation in DXB-treated RAW 264.7 cells, suggesting the prevention of DXB-induced apoptosis. LPS did not significantly inhibit DXB-induced DNA damages detected by a single cell gel electrophoresis (comet) assay. LPS definitely inhibited the stabilization and nuclear translocation of p53 in DXB-treated RAW 264.7 cells. LPS as well as an inhibitor of p53 abolished DXB-induced apoptosis. Therefore, p53 was suggested to play a pivotal role in the prevention of DXB-induced apoptosis in RAW 264.7 cells by LPS.