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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

张庆林, 吴祖泽, 曹菊荣, 薛惠华, 裴雪涛, 王立生, 徐黎, 杜泽涵, 冯锐

(北京放射医学研究所，北京100850)

摘要

胎儿组织中存在低分子肿瘤抑制物。胎肝细胞的甲醇一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、Sephadex LH-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-(}-轻基胆固醇(7-(}-hydroxycholesterol, 7-(3-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一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15 pg/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-(3-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。

关键词： 胎儿肝脏; 低分子抑瘤物; 分离; 结构鉴定; 7-酮基胆固醉; 7-#beta#羟经基胆固醇

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

ZHANG QING-LIN, WU ZU-ZE (WU CHUTSE), CAO JU-RONG, XUE HUI-HUA, PEI XUE-TAO, WANG LI-SHENG , XU LI, DU ZE-HAN, FENG RuI,

Beijing Institute of Radiation Medicine, Beijing 100850)

Abstract

Our previous work showed the existence of low molecular weight tumor suppres-
sors in human fetal tissues. In this paper，two tumor cell suppressors were isolated and purified from methanol extract of human fetal liver by C18 reversed-phase medium pressure chromatography，gel filtration on Sephadex LH-20，and high-performance liquid chromatography，directed by suppression of growth of HL-60 cells. The structures of the suppressors were identified to be 7-ketocholesterol and 7-(3-hydroxycholesterol. Under the condition of in vitro agar plate culture，7-ketocholesterol and 7-卜hydroxycholesterol showed preferentially inhibitory effects on the growth of both human and
murine 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 granulocyte
macrophage progenitors (CFU-GM)

Key words: human fetal liver;low molecular weight tumor suppressor;separation;structure identification;7-ketocholesterol;7#beta#-hydroxycholesterol

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引用本文：

张庆林, 吴祖泽, 曹菊荣, 薛惠华, 裴雪涛, 王立生, 徐黎, 杜泽涵, 冯锐. 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[J]. 生理学报 1997; 49 (2): .

ZHANG QING-LIN, WU ZU-ZE (WU CHUTSE), CAO JU-RONG, XUE HUI-HUA, PEI XUE-TAO, WANG LI-SHENG , XU LI, DU ZE-HAN, FENG RuI,. STUDIES ON THE ISOLATION，STRUCTURE IDENTIFICATION AND BIOLOGICAL FUNCTION OF TWO TUMOR CELL SUPPRESSORS OF HUMAN FETAL LIVER ORIGIN . Acta Physiol Sin 1997; 49 (2): (in Chinese with English abstract).