期刊
BRITISH JOURNAL OF CANCER
卷 85, 期 8, 页码 1185-1192出版社
CHURCHILL LIVINGSTONE
DOI: 10.1054/bjoc.2001.2055
关键词
Fas-L; ribozyme; tumorigenesis; glioma
类别
Fas-L (CD95L, APO-IL) expresses in a variety of tumours; and has been proposed to play a role in tumour formation and metastasis. The contribution of Fas-L to tumour growth, however, is not conclusive especially in systems using cells with over-expressed Fas-L. In this study we down-regulated the expression o Fas-L in human glioma cells by a hammerhead ribozyme (Fas-L-ribozyme) 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-carrying cells grew faster with lesser apoptosis, formed bigger tumour with significantly fewer infiltrating cells in the tumour area, and triggered relatively milder tumour-associated liver damage than vector controls did. Thus, down-regulation of Fas-L not only improved viability of glioma cells but also reduces local immune responses that may consequently affect tumour formation. Taken together, our findings imply that endogenous expression of Fas-L in malignant cells is not always growth promoting. (C) 2001 Cancer Research Campaign.
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