Open AccessLysosome Labilizers Potentiate the Antitumor Effects of Tumor Necrosis Factor‐α
Author(s) -
Masegi Tsukio,
Kato Arata,
Kitai Kazuo,
Fukuoka Masami,
Soma Kazuhiko,
Ichikawa Yataro,
Nakamura Satoshi,
Watanabe Naoki,
Niitsu Yoshiro
Publication year - 1993
Publication title -
japanese journal of cancer research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 0910-5050
DOI - 10.1111/j.1349-7006.1993.tb00157.x
Subject(s) - tumor necrosis factor alpha , plasminogen activator , in vivo , cytotoxicity , cytotoxic t cell , medicine , t plasminogen activator , necrosis , ratón , activator (genetics) , lysosome , in vitro , endocrinology , pharmacology , immunology , biology , enzyme , biochemistry , receptor , microbiology and biotechnology
Enhancement of in vitro cytotoxic activity of tumor necrosis factor‐ α (TNF‐ α ) was observfed in combination with lysosome labilizers, particularly with urokinase‐type plasminogen activator (u‐PA), tissue‐type plasminogen activator (t‐PA) and lipoprotein lipase (LPL). The concentration of TNF‐ α resulting in 50% cytotoxicity to L929 cells was only 20–30% of the value for TNF‐ α alone, when used in combination with a nontoxic dose of u‐PA, t‐PA or LPL. Furthermore, combined intravenous (i.v.) administration of TNF‐ α (3.5 × 10 5 U/mouse) and u‐PA (300 IU/mouse) markedly increased the in vivo antitumor activity of TNF‐ α to Meth A tumors transplanted into BALB/c mice; the tumor weight in co‐administered mice was about 40% of that in mice given TNF‐ α alone on day 6. The combination therapy of TNF‐ α (7.0 × 10 4 U/mouse, i.v.) and u‐PA (300 IU/mouse, i.v.) was also effective for L929 tumors in Crj:CD‐1(1CR)‐nu nude mice compared with the conventional therapy with TNF‐ α alone. These results suggest that the combination of TNF‐ α and lysosome labilizers is a promising antitumor therapeutic regimen with clinical potential.