Hassan Ferdaus, Islam Shamima, Mu Mya Mya, Ito Hiroyasu, Koide Naoki, Mori Isamu, Yoshida Tomoaki, Yokochi Takashi
Department of Microbiology and Immunology, School of Medicine, Aichi Medical University, Nagakute, Aichi 480-1195, Japan.
Mol Cancer Res. 2005 Jul;3(7):373-9. doi: 10.1158/1541-7786.MCR-05-0046.
The effect of lipopolysaccharide on doxorubicin-induced cell death was studied by using mouse RAW 264.7 macrophage cells. Pretreatment with lipopolysaccharide at 10 ng/mL prevented doxorubicin-induced cell death and the inhibition was roughly dependent on the concentration of lipopolysaccharide. Posttreatment with lipopolysaccharide for 1 hour also prevented doxorubicin-induced cell death. Lipopolysaccharide inhibited DNA fragmentation and caspase-3 activation in doxorubicin-treated RAW 264.7 cells, suggesting the prevention of doxorubicin-induced apoptosis. Lipopolysaccharide did not significantly inhibit doxorubicin-induced DNA damage detected by single-cell gel electrophoresis (comet) assay. Lipopolysaccharide definitely inhibited the stabilization and nuclear translocation of p53 in doxorubicin-treated RAW 264.7 cells. Lipopolysaccharide, as well as being an inhibitor of p53, abolished doxorubicin-induced apoptosis. Therefore, p53 was suggested to play a pivotal role in the prevention of doxorubicin-induced apoptosis in RAW 264.7 cells by lipopolysaccharide.
通过使用小鼠RAW 264.7巨噬细胞研究了脂多糖对阿霉素诱导的细胞死亡的影响。用10 ng/mL脂多糖预处理可防止阿霉素诱导的细胞死亡，且这种抑制作用大致取决于脂多糖的浓度。用脂多糖后处理1小时也可防止阿霉素诱导的细胞死亡。脂多糖抑制了阿霉素处理的RAW 264.7细胞中的DNA片段化和半胱天冬酶-3激活，提示可防止阿霉素诱导的细胞凋亡。脂多糖对单细胞凝胶电泳（彗星）试验检测到的阿霉素诱导的DNA损伤没有显著抑制作用。脂多糖确实抑制了阿霉素处理的RAW 264.7细胞中p53的稳定和核转位。脂多糖作为p53的抑制剂，消除了阿霉素诱导的细胞凋亡。因此，提示p53在脂多糖预防RAW 264.7细胞中阿霉素诱导的细胞凋亡中起关键作用。
