氧代赖氨酸对肝癌细胞生长、AFP分泌及γ-GT活性的抑制作用  

Inhibitory effect of L4oxalysine on the growth, AFP secretion and GT activity of human hepatoma cells

作　　者：章雄文[1] 胥彬[1] 

机构地区：[1]中国科学院上海药物研究所

出　　处：《中国药理学通报》1999年第2期131-134,共4页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金

摘　　要：目的研究氧代赖氨酸（Ｌ４ｏｘａｌｙｓｉｎｅ，ＯＸＬ）对人肝癌细胞体内、外生长及其对甲胎蛋白（ＡＦＰ）分泌和γ谷氨酰转肽酶（γＧＴ）活性的影响。方法以ＭＴＴ法测定ＯＸＬ的体外抗肝癌活性。以裸小鼠异种移植人肝癌模型观察药物的体内抗肝癌作用。以酶联免疫法（ＥＬＩＳＡ）检测ＡＦＰ水平。以酶底物法检测γＧＴ活力。结果①ＯＸＬ０８～６８×１０－４ｍｏｌ·Ｌ－１作用６ｄ，对体外培养的３种人肝癌ＨｅｐＧ２、Ｂｅｌ７４０２和Ｂｅｌ７４０４细胞株仅有微弱的生长抑制作用，６８×１０－４ｍｏｌ·Ｌ－１时的抑制率为１３７％～４５６％。②ＯＸＬ２００ｍｇ·ｋｇ－１，ｐｏ，ｑｄ×２ｗｋ对裸小鼠异种移植人ＨＣＣ９３实体型肝癌的生长有明显抑制作用，抑瘤率为４３５％（Ｐ＜００５）。③ＯＸＬ能明显抑制人肝癌细胞ＡＦＰ分泌量和γＧＴ酶活力，丝裂霉素Ｃ在治疗剂量时能明显抑制人肝癌的生长，并使γＧＴ的活性显著降低，但对ＡＦＰ的抑制作用却较弱。结论ＯＸＬ的体内抗人肝癌活性较体外强，其作用与１９９８０６２４收稿，１９９８１１１８修回国家自然科学基金资助项目，Ｎｏ３９５７０８２４作者简介：章雄文，男，３４岁，博士?AIM To study the effect of L4oxalysine (OXL) on the growth, fetoprotein (AFP) secretion and glutamyltranspeptidase (GT) activity of human hepatoma cells in vitro and in vivo. METHODS Antihepatoma activity in vitro was determined by MTT method. Antihepatoma effect in vivo was studied in nude mice bearing human hepatoma. AFP was assayed by ELISA and GT was determined by enzymesubstrate method. RESULTS After using 086810-4molL-1of OXL for 6 d, the growth of the human hepatoma HepG2, Bel7402 and Bel7404 cells cultured in vitro was slightly inhibited. At the concentration of 6810-4molL-1, the inhibition rate was 137%456%. OXL 200 mgkg-1, po, qd2 wk could obviously inhibit the growth of HCC93 human hepatoma transplanted into nude mice with inhibitory rate of 435% (P<005). OXL significantly inhibited the secretion of AFP and the activity of GT of human hepatoma cells. Mitomycin C at the therapeutic dose could inhibit the growth of human hepatoma cells and decrease the GT activity significantly but produce slighter inhibitory effect on AFP secretion of hepatoma cells. CONCLUSION The antihepatoma activity of OXL in vivo is stronger than that in vitro and its mechanism of action was related to the inhibition of AFP secration and GT activity of human hepatoma cells.

关 键 词：氧代赖氨酸 肝肿瘤 甲胎蛋白 药物疗法 Γ-GT 

分 类 号：R979.14[医药卫生—药品] R735.705[医药卫生—药学]