Combined effects of synthetic lipid A analogs or bacterial lipopolysaccharide with glucosaminylmuramyl dipeptide on antitumor activity against Meth A fibrosarcoma in mice.
The combined effects of the synthetic glucosaminylmuramyl dipeptide (GMDP) on the antitumor activity of chemically synthesized lipid A analogs, compound A-103 (glucosamine-4-phosphate with (R)-3-tetradecanoyloxytetradecanoyl group at the C-2 and C-3 positions), Escherichia coli-type lipid A (506), Salmonella typhimurium LT-2 lipopolysaccharide (LPS) against Meth A fibrosarcoma in mice were examined. Meth A fibrosarcoma cells (5 x 10(5) were inoculated intradermally into BALB/c mice on day 0, and compound A-103 and/or GMDP was administered intravenously (i.v.) on days 7 and 9. Two i.v. injections of A-103 (50 micrograms) alone or GMDP (10 micrograms) alone induced 42.8 or 51.8% inhibition of the rate of tumor growth, however, A-103 (100 micrograms) with GMDP (10 micrograms) exhibited a high 68.7% inhibition rate 19 days after tumor inoculation. The inhibition of the tumor growth rate by the combination A-103 (100 micrograms) or 506 (50 micrograms) with GMDP (10 micrograms) was stronger than that of A-103 or 506 with MDP (10 micrograms). The combination of LPS (1 or 10 micrograms) with GMDP (10 micrograms) exhibited a higher inhibition rate than that of LPS with MDP, and three or four tumor-free mice out of five mice were observed, suggesting that the combined effect of GMDP is more potent than that of MDP. With the addition of GMDP, A-103 did not enhance the production of tumor necrosis factor (TNF) on the basis of L929 cell lysis.(ABSTRACT TRUNCATED AT 250 WORDS)
Shimizu
T
T
Department of Microbiology, University of Shizuoka, School of Pharmaceutical Sciences, Japan.
Iwamoto
Y
Y
Yanagihara
Y
Y
Ikeda
K
K
Achiwa
K
K
D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D005354:Fibrosarcoma / Q000139:chemically induced / Q000188:drug therapy*; D008050:Lipid A / Q000008:administration & dosage* / Q000031:analogs & derivatives; D008070:Lipopolysaccharides / Q000008:administration & dosage*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D000276:Adjuvants, Immunologic; D008050:Lipid A; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D000119:Acetylmuramyl-Alanyl-Isoglutamine; C063429:glucosaminylmuramyl-2-alanine-D-isoglutamine