COMBINED EFFECTS OF SYNTHETIC LIPID A ANALOGS AND MURAMYL DIPEPTIDE ON ANTITUMOR-ACTIVITY AGAINST METH A FIBROSARCOMA IN MICE

被引:0
|
作者
SHIMIZU, T
OHTSUKA, Y
YANAGIHARA, Y
ITOH, H
NAKAMOTO, SI
ACHIWA, K
机构
[1] FUJI CHEM IND CO LTD, TOYAMA 933, JAPAN
[2] UNIV SHIZUOKA, SCH PHARMACEUT SCI, DEPT MED CHEM, OYA, SHIZUOKA 422, JAPAN
来源
INTERNATIONAL JOURNAL OF IMMUNOPHARMACOLOGY | 1991年 / 13卷 / 05期
关键词
D O I
暂无
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Combined effects of chemically synthesized lipid A analogs, the compound A-171 (acylglucosamine-4-phosphate with (R)-3-hydroxytetradecanoyl and (R)-3-hydroxytetradecanoyloxytetradecanoyl group at the C-2 and C-3 positions), or the compound A-172 (with (R)-3-hydroxytetradecanoyloxytetradecanoyl 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-mu-g/mouse) with MDP (10-mu-g) was weaker than that of 50-mu-g of synthetic lipid A analogs (506), or 10-mu-g 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-mu-g) with MDP (10-mu-g) 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.
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页码:605 / 611
页数:7
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