Shimizu M, Yoshimoto T, Nagata S, Matsuzawa A
Department of Cancer Therapeutics, Tokyo Metropolitan Institute of Medical Science, Japan.
Biochem Biophys Res Commun. 1996 Nov 12;228(2):375-9. doi: 10.1006/bbrc.1996.1669.
We tried to induce tumor cell death in vivo through Fas (CD95)-mediated apoptosis. Murine hepatoma MH 134 (Fas-) was transfected with murine Fas antigen cDNA. Fas+ F6b but not Fas- N1d cells underwent apoptosis after treatment with anti-Fas antibody in vitro. The possibility of eradicating tumor cells in vivo with anti-Fas antibody was investigated using double-mutant gld/gld lpr/lpr mice which lack both Fas ligand (FasL) and Fas to avoid cytotoxic activity of the antibody to the liver and interference from endogenous FasL. A single administration of anti-Fas antibody efficiently suppressed the growth of F6b tumors but not that of N1d tumors in these mice. Thus, the therapy with Fas-FasL system may be a promising approach for cancer treatment, and this model is useful for study on in vivo apoptosis-mediated antitumor activity.
我们试图通过Fas（CD95）介导的凋亡在体内诱导肿瘤细胞死亡。用小鼠Fas抗原cDNA转染小鼠肝癌MH 134（Fas-）。Fas+ F6b细胞而非Fas- N1d细胞在体外经抗Fas抗体处理后发生凋亡。使用既缺乏Fas配体（FasL）又缺乏Fas的双突变gld/gld lpr/lpr小鼠，研究用抗Fas抗体在体内根除肿瘤细胞的可能性，以避免抗体对肝脏的细胞毒活性以及内源性FasL的干扰。在这些小鼠中，单次给予抗Fas抗体可有效抑制F6b肿瘤的生长，但不能抑制N1d肿瘤的生长。因此，Fas-FasL系统疗法可能是一种有前景的癌症治疗方法，并且该模型对于研究体内凋亡介导的抗肿瘤活性很有用。
