Zhang G M, Feng Z H, Li D, Zhang H
Department of Medical Molecular Biology, Tongji Medical University, Wuhan 430030, China.
Acta Pharmacol Sin. 2000 Jun;21(6):567-70.
To investigate the characterization of pharmacological action & of CH50, a recombinant polypeptide of human fibronectin, by comparing the effects of CH50 on macrophage activation and its anti-tumor activity with those of lipopolysaccharides (LPS).
The production of nitric oxide (NO) as an index macrophage activation was determined by colorimetric assay. The interferon-gamma (IFN-gamma) transfection was performed with coprecipitation of calcium phosphate and DNA. The melanoma B16 cells were inoculated into abdominal cavity of mice and the number of tumor nodes was recorded.
At lower concentrations or when given alone in vitro, CH50 produced ten times less NO than LPS (P < 0.01). But at concentrations higher than 1 mg.L-1, CH50 activated the IFN-gamma-primed macrophages to produce NO to the same extent as LPS (P > 0.05). There was no synergism between CH50 and LPS. Both CH50 and LPS alone could reduce the number of tumor nodes in abdominal cavity of mice but CH50 had a stronger inhibitory effect on the growth of tumor in vivo as compared to LPS (P < 0.01). CH50/IFN-gamma had also a better inhibitory effect on tumor growth in vivo than LPS/IFN-gamma did.
In the presence of IFN-gamma, the ability of CH50 to activate macrophages is the same as that of LPS. But CH50 has better antitumorogenic effects in vivo against mouse melanoma as compared to LPS.
通过比较重组人纤连蛋白多肽CH50与脂多糖(LPS)对巨噬细胞激活作用及其抗肿瘤活性的影响,研究CH50的药理作用特性。
采用比色法测定一氧化氮(NO)的生成作为巨噬细胞激活的指标。采用磷酸钙与DNA共沉淀法进行干扰素-γ(IFN-γ)转染。将黑色素瘤B16细胞接种于小鼠腹腔,记录肿瘤结节数量。
在较低浓度或体外单独给药时,CH50产生的NO比LPS少10倍(P<0.01)。但在浓度高于1mg.L-1时,CH50激活IFN-γ预处理的巨噬细胞产生NO的程度与LPS相同(P>0.05)。CH50与LPS之间无协同作用。CH50和LPS单独使用均可减少小鼠腹腔内肿瘤结节数量,但与LPS相比,CH50对体内肿瘤生长的抑制作用更强(P<0.01)。CH50/IFN-γ对体内肿瘤生长的抑制作用也比LPS/IFN-γ更好。
在IFN-γ存在的情况下,CH50激活巨噬细胞的能力与LPS相同。但与LPS相比,CH50对小鼠黑色素瘤的体内抗肿瘤作用更好。