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-1L) 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.
Chio
C C
CC
Department of Neurosurgery, Chi-Mei Foundation Hospital, Tainan, Taiwan.
Wang
Y S
YS
Chen
Y L
YL
Lin
S J
SJ
Yang
B C
BC
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D015536:Down-Regulation; D053222:Fas Ligand Protein; D005910:Glioma / Q000209:etiology* / Q000473:pathology; D006801:Humans; D008099:Liver / Q000473:pathology*; D008297:Male; D008562:Membrane Glycoproteins / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D016337:RNA, Catalytic / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
C505661:FASLG protein, human; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D008562:Membrane Glycoproteins; D016337:RNA, Catalytic