Down-regulation of Fas-L in glioma cells by ribozyme reduces cell apoptosis, tumour-infiltrating cells, and liver damage but accelerates tumour formation in nude mice

Fas-L (CD95L, APO-IL) expresses in a variety of tumours; and has been propo sed to play a role in tumour formation and metastasis. The contribution of Fas-L to tumour growth, however, is not conclusive especially in systems us ing cells with over-expressed Fas-L. In this study we down-regulated the ex pression o Fas-L in human glioma cells by a hammerhead ribozyme (Fas-L-ribo zyme) targeting against Fas-L mRNA. Fas-L-ribozyme-carrying cells exhibited slightly enhanced growth rate and less degree of spontaneous apoptosis in vitro as compared with vector controls. In nude mice, Fas-L-ribozyme-carryi ng cells grew faster with lesser apoptosis, formed bigger tumour with signi ficantly fewer infiltrating cells in the tumour area, and triggered relativ ely milder tumour-associated liver damage than vector controls did. Thus, d own-regulation of Fas-L not only improved viability of glioma cells but als o reduces local immune responses that may consequently affect tumour format ion. Taken together, our findings imply that endogenous expression of Fas-L in malignant cells is not always growth promoting. (C) 2001 Cancer Researc h Campaign.