人胎肝中两种抑制肿瘤细胞生长活性成分的分离鉴定及功能研究

STUDIES ON THE ISOLATION, STRUCTURE IDENTIFICATION AND BIOLOGICAL FUNCTION OF TWO TUMOR CELL SUPPRESSORS OF HUMAN FETAL LIVER ORIGIN

胎儿组织中存在低分子肿瘤抑制物。胎肝细胞的甲醇-丙酮提取物中保留有大部分抑瘤活性。用体外液体培养条件下对人急性粒系白血病细胞系（HL-60）的抑制作用为指标，跟踪分离过程。提取物经反相C18中压液相色谱、SephadexLH-20凝胶色谱及正相高效液相色谱分离得到两种活性物质，经NMR和HRMS鉴定为7-酮基胆固醇（7-ketocholesterol，7-KC）和7-β-羟基胆固醇（7-β-hydroxycholesterol，7-β-HC）。体外琼脂培养条件下7-KC对小鼠S-180细胞较对正常小鼠骨髓粒-巨噬系祖细胞有更强的抑制增殖及集落生成作用。7-KC在浓度15μg／ml之内对正常人骨髓CFU-GM基本无抑制作用，但对HL-60细胞却有明显的抑制增殖作用，7-β-HC对HL-60细胞增殖较对正常人骨髓CFU-GM有更强的抑制作用。

Our previous work showed the existence of low molecular weight tumor suppressors in human fetal tissues. In this paper, two tumor cell suppressors were isolated andpurified from methanol extract of human fetal liver by C18 reversed-phase mediumpressure chromatography, gel filtration on Sephadex LH-20, and high-performance liquid chromatography, directed by suppression of growth of HL-60 cells. The structuresof the suppressors were identified to be 7-ketocholesterol and 7-β-hydroxycholesterol.Under the condition of in vitro agar plate culture, 7--ketocholesterol and 7-β-hydroxycholesterol showed preferentially inhibitory effects on the growth of both human andmurine leukemic cell lines including human HL-60 and murine S-180 cells, but less effective on the growth of normal human and murine bone marrow granulocytemacrophage progenitors (CFU-GM).