Effect of transfection with human interferon-beta gene entrapped in cationic multilamellar liposomes in combination with 5-fluorouracil on the growth of human esophageal cancer cells in vitro.
When human esophageal cancer cells were transfected with the human interferon-beta (hIFN-beta) gene entrapped in cationic multilamellar liposomes, the growth of all cancer cells tested was suppressed in a dose-dependent manner. The 50% inhibitory concentration (IC50) of the hIFN-beta gene entrapped in the liposomes ranged from 16 to 176 ng plasmid DNA/ml culture medium. Among the 10 cell lines examined, NUEC3, NUEC4, TE-3 and WSSC cell lines were highly susceptible to transfection with this gene entrapped in the liposomes. The IC50 values of the hIFN-beta gene entrapped in the liposomes with respect to cell growth were positively-correlated with those of exogenous cytokine hIFN-beta, suggesting that the antiproliferative effect of hIFN-beta gene entrapped in the liposomes can be mainly ascribed to the function of hIFN-beta produced by cells transfected with the gene. Two days after transfection with the liposome-entrapped gene, the concentration of hIFN-beta secreted into the medium was determined. Even though the level of hIFN-beta observed in the medium was lower than that of the IC50 of exogenously added hIFN-beta, the inhibitory potency of the hIFN-beta gene entrapped in the liposomes on the cell growth was remarkable. When the esophageal cancer cells were treated with 5-fluorouracil (5-FU) in the presence of a low concentration of liposome-entrapped-gene, the rate of growth inhibition of these cells increased over that caused by either 5-FU or hIFN-beta gene entrapped in the liposomes alone. All these data suggest that combination therapy with the hIFN-beta gene entrapped in cationic multilamellar liposomes and the anticancer drug 5-FU would be beneficial for preoperative treatment of carcinoma of the esophagus.
Tsunoo
Hideo
H
Department of Surgery II, Nagoya University School of Medicine, Japan. tsunoo@tsuru.med.nagoya-u.ac.jp
Komura
Sadaaki
S
Ohishi
Nobuko
N
Yajima
Haruyoshi
H
Akiyama
Seiji
S
Kasai
Yasushi
Y
Ito
Katsuki
K
Nakao
Akimasa
A
Yagi
Kunio
K
D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D003131:Combined Modality Therapy; D004938:Esophageal Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D005472:Fluorouracil / Q000494:pharmacology*; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D020128:Inhibitory Concentration 50; D016899:Interferon-beta / Q000235:genetics*; D008081:Liposomes; D014162:Transfection / Q000379:methods; D014407:Tumor Cells, Cultured
D000964:Antimetabolites, Antineoplastic; D008081:Liposomes; D016899:Interferon-beta; D005472:Fluorouracil