Combined effects of synthetic lipid A analogs and muramyl dipeptide on antitumor activity against Meth A fibrosarcoma in mice

• Published in: International journal of immunopharmacology Vol. 13; no. 5; p. 605
• Main Authors: Shimizu, T, Ohtsuka, Y, Yanagihara, Y, Itoh, H, Nakamoto, S, Achiwa, K
• Format: Journal Article
• Language: English
• Published: England 1991
• Subjects: Acetylmuramyl-Alanyl-Isoglutamine - pharmacology; Animals; Antineoplastic Combined Chemotherapy Protocols - pharmacology; Drug Screening Assays, Antitumor; Fibrosarcoma - drug therapy; Injections, Intradermal; Lipid A - analogs & derivatives; Lipid A - chemistry; Lipid A - pharmacology; Male; Mice; Mice, Inbred BALB C; Mice, Inbred C3H; Tumor Cells, Cultured
• ISSN: 0192-0561
• DOI: 10.1016/0192-0561(91)90083-J

Combined effects of chemically synthesized lipid A analogs, the compound A-171 (acylglucosamine-4-phosphate with (R)-3-hydroxytetradecanoyl and (R)-3-hydroxytetradecanoyloxy]tetradecanoyl group at the C-2 and C-3 positions), or the compound A-172 (with (R)-3-hydroxytetradecanoyloxy]tetradecanoyl and (R)-3-tetradecanoyloxytetradecanoyl group at the C-2 and C-3 positions), and muramyl dipeptide (MDP) on antitumor activity against Meth A fibrosarcoma, were examined. Meth A fibrosarcoma cells (5 X 10(5)) were inoculated intradermally into BALB/c mice on day 0, compound A-172 and/or MDP were administered intravenously (i.v.) on day 7. Although the antitumor activity by single i.v. injection of A-172 (50 micrograms/mouse) with MDP (10 micrograms) was weaker than that of 50 micrograms of synthetic lipid A analogs (506), or 10 micrograms of bacterial lipopolysaccharide (LPS) with MDP, A-172 alone and with MDP exhibited tumor inhibition rates of 49.0 and 70.6%, respectively. When A-171 (50 micrograms) with MDP (10 micrograms) was administered i.v. twice (days 7 and 10) into mice inoculated Meth A fibrosarcoma, two of five mice caused complete tumor regression. Furthermore, L929 cell lysis by the combination of A-171, A-172 with MDP was higher than that by the analogs or MDP alone, suggesting that the lipid A analogs of monosaccharide type as well as LPS are able to enhance the production of tumor necrosis factor in the presence of MDP.