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)