Delivery of interferon to intracellular pathways by encapsulation of interferon into multilamellar liposomes is independent of the status of interferon receptors.
The antiproliferative effect of interferon alpha (IFN-alpha) against cultured 253J human bladder tumour cells was enhanced when IFN-alpha was encapsulated into multilamellar phospholipid liposomes (MLV). Moreover, significant cytostasis of a variant 253J subline (253J alpha R, resistant to the antiproliferative effect of IFN-alpha), could be achieved by delivery of IFN-alpha contained in liposomes. Although the two cell lines have the same number and affinity of cell receptors for IFN-alpha, the 253J alpha R cells did not down-regulate receptors as observed for the IFN-sensitive 253J cells. The IFN-response genes, 2'-5' oligosynthetase and gene 6-16 were equally induced in both cell lines following incubation of the cells with either free IFN-alpha or liposome-encapsulated IFN-alpha. Incorporation of radiolabelled IFN-alpha into cells by liposomes was independent of the status of IFN-receptors (the receptors being either occupied or down-regulated). These observations are consistent with the hypothesis that the antiproliferative effects of IFN-alpha against 253J and 253J alpha R cells may be mediated by internalization of IFN-alpha.
Killion
J J
JJ
Department of Cell Biology, University of Texas M.D. Anderson Cancer Center, Houston.
Fishbeck
R
R
Bar-Eli
M
M
Chernajovsky
Y
Y
D015088:2',5'-Oligoadenylate Synthetase / Q000235:genetics; D015536:Down-Regulation / Q000187:drug effects; D004337:Drug Carriers; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage*; D008081:Liposomes; D053633:Receptor, Interferon alpha-beta; D017471:Receptors, Interferon / Q000187:drug effects*; D015398:Signal Transduction / Q000187:drug effects*; D014407:Tumor Cells, Cultured; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy*
D004337:Drug Carriers; D016898:Interferon-alpha; D008081:Liposomes; D017471:Receptors, Interferon; D053633:Receptor, Interferon alpha-beta; D015088:2',5'-Oligoadenylate Synthetase