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机构地区:[1]中国人民解放军第一军医大学药物研究所,广东广州510515
出 处:《肿瘤防治杂志》2004年第1期11-14,共4页China Journal of Cancer Prevention and Treatment
基 金:国家"10 3 5"工程重大项目资助 (96-90 1-0 1-5 2 )
摘 要:目的 :研究盐酸洛拉曲克 (nola trexeddihydrochloride ,NLTX)在体外对正常人胚肝细胞Fb和人HepG2、QSG770 3肝癌细胞株以及小鼠S180肉瘤细胞株的抗增殖作用 ;探讨其在荷S180肉瘤小鼠组织中的分布情况。方法 :四氮唑盐 (MTT )法测定NLTX在体外对细胞的抗增殖作用 ,高效液相色谱法测定在荷S180肉瘤小鼠血液、肝脏和肉瘤组织中NLTX的浓度。结果 :NLTX在体外对HepG2、QSG770 3以及S180肿瘤细胞株的半数抑制浓度分别为2 17、0 61及 0 72 μg/mL ,对正常人胚肝细胞Fb则为 82 60 μg/mL ;以 10 0mg/kg剂量单次灌胃给药后 ,NLTX在小鼠血、肝及肉瘤组织中可达到的最高浓度分别为(18 2 4± 5 68)、 (4 0 12± 16 81)和(16 0 8± 7 64 ) μg/mL。 结论 :NLTX在体外有显著的抗细胞增殖作用 ,对肿瘤细胞的作用强度高于正常细胞 ,对肿瘤细胞的抑制作用有选择性 ;该化合物在小鼠组织中可以达到有效的治疗浓度。OBJECTIVES:To evaluate the anti proliferation effect of nolatrexed dihydrochloride (NLTX) on normal human embryo liver cell Fb and on human liver cancer cell lines HepG2 and QSG7703,and its anti proliferation effect on mouse sarcoma cell line S180 in vitro .Distribution of the compound in mice with S180 sarcoma was also studied.METHODS:Anti proliferation effect of NLTX in vitro was assayed by MTT,while the drug concentration in blood,liver and sarcoma tissues of the mice were assayed by the high performance liquid chromatography.RESULTS:Fifty percent inhibition concentration of NLTX on cancer cell lines HepG2,QSG7703 and S180 were 2 17,0 61 and 0 72 μg/mL respectively;On the counterpart,the value was 82 60 μg/mL for the normal human liver cell,and the maximum concentration of the agent in blood,liver and solid tumor tissues reached (18 24±5 68),(40 12±16 81) and (16 08±7 64) μg/mL after a single oral administration of 100 mg/kg respectively.CONCLUSIONS:Anti proliferation effects of NLTX on cancer cells were significant,and the harm which the agent done to normal cell was much slight.We can assume that this property will lead to a selective anti cancer effect in clinic.At the same time,the concentration of NLTX in mouse tissues could reach a high level which will surpass the IC 50 for cancer cells much.
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