Li Wenzhu, Wang Shengyu, Chen Caixia, Zhuang Guohong
Anti-Cancer Research Center, Medical College [corrected] Xiamen University, Xiamen, Fujian 361005, China.
Cell Mol Immunol. 2006 Dec;3(6):467-71.
The apoptosis inducing effects on tumor cell lines MGC803, BEL7402 and HL60 by Fas ligand and anti-human DR5 monoclonal antibodies (anti-DR5 mAb) and the underlying mechanism was studied. Fas/DR5 mRNA was detected by RT-PCR. Cytotoxicity exerted by FasL/anti-DR5 mAb on tumor cell lines was measured by MTT assay and the induced apoptosis was determined by agarose gel electrophoresis. Flow cytometry was employed to analyze the mode of cell death. The mRNA expression of DR5 in MGC803 and BEL7402 cells after giving anti-DR5 mAb was up-regulated compared with control group, while it was down-regulated in HL60 cells in the same condition. The mRNA expression of Fas in HL60 was higher after giving FasL compared with control group, while it was lower in MGC803 and BEL7402. MGC803 and BEL7402 were sensitive to anti-DR5 mAb but partially to FasL, and HL60 was sensitive to FasL but less sensitive to anti-DR5 mAb. Apoptosis induced by Fas ligand and anti-DR5 mAb vary among tumor cell lines. The underlying mechanism may be relevant to Fas/DR5 mRNA expression, which was presented as the release of caspase-8 and Bcl-2.
研究了Fas配体和抗人DR5单克隆抗体（抗-DR5 mAb）对肿瘤细胞系MGC803、BEL7402和HL60的凋亡诱导作用及其潜在机制。通过RT-PCR检测Fas/DR5 mRNA。采用MTT法检测FasL/抗-DR5 mAb对肿瘤细胞系的细胞毒性，通过琼脂糖凝胶电泳测定诱导的凋亡。运用流式细胞术分析细胞死亡模式。给予抗-DR5 mAb后，MGC803和BEL7402细胞中DR5的mRNA表达与对照组相比上调，而在相同条件下HL60细胞中则下调。给予FasL后，HL60中Fas的mRNA表达高于对照组，而在MGC803和BEL7402中则较低。MGC803和BEL7402对抗-DR5 mAb敏感但对FasL部分敏感，HL60对FasL敏感但对抗-DR5 mAb不太敏感。Fas配体和抗-DR5 mAb诱导的凋亡在不同肿瘤细胞系中有所不同。潜在机制可能与Fas/DR5 mRNA表达有关，表现为caspase-8和Bcl-2的释放。
