洛拉曲克在体内外对SRS-82细胞株的抗增殖作用  

Antiproliferative effect of nolatrexed on cell line SRS-82 in vitro and in vivo

作　　者：赵爱国[1] 刘叔文[1] 徐继红[1] 吴曙光[1] 

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：《中国新药与临床杂志》2004年第8期489-492,共4页Chinese Journal of New Drugs and Clinical Remedies

基　　金：国家"10 35"工程重大项目资助 (96 90 1 0 1 5 2 )

摘　　要：目的 :研究全合成新型胸苷合成酶抑制药洛拉曲克 (nolatrexed)在体内、外对SRS 82细胞株及正常人胚肾HEK2 93细胞的抗增殖作用。方法 :四氮唑盐 (MTT)法测定抑制率 ;以提高荷腹水瘤小鼠存活时间及荷实体瘤瘤重减轻情况为指标考察洛拉曲克对SRS 82所致肿瘤的治疗作用。结果 :在体外洛拉曲克对SRS 82肿瘤细胞株有较强的细胞毒作用 ,对正常细胞HEK2 93抑制作用较弱 (P <0 .0 1) ;体内实验显示洛拉曲克可明显提高荷腹水瘤小鼠的存活时间 ,减轻荷实体瘤小鼠的瘤重 ,洛拉曲克松低剂量组与氟尿嘧啶 (10mg·kg- 1)相当 (P >0 .0 5 )高剂量组 (P <0 .0 1)。结论 :洛拉曲克在体内外对SRS 82肿瘤细胞有显著的抗增殖作用 ,在体外对肿瘤细胞具有选择性的抗增殖作用。AIM: To evaluate the antiproliferative effect of nolatrexed,a novel thymidylate synthase inhibitor,on mouse cancer cell line SRS-82 in vitro and in vivo and on normal human embryo kidney cell HEK293. METHODS: Inhibition rate of the compound on the cultured cancer cell line SRS-82 and human embryo kidney cell HEK293 were assayed by MTT method. Antineoplasms effects on the mice with SRS-82 ascitic type of carcinoma and solid tumor were evaluated by survival time escalation and the weight reduction of the tumor tissue respectively. RESULTS: The antiproliferative effect of nolatrexed on cancer cell and normal cell was selective in vitro . The inhibitory potency of the compound on cancer cell SRS-82 was more powerful than that on the normal cell HEK293( P <0.01).The mean survival time of the mice with ascitic type of carcinoma was increased significantly when treated with moderate dosage of nolatrexed (75 mg·kg -1 ) comparing to that of fluorouracil(10 mg·kg -1 )or other levels of the same compound ( P <0.01). While treated the mice with solid tumor,the effects of high(100 mg·kg -1 ) and moderate (75 mg·kg -1 ) dosage of the compound were more potent than that of fluorouracil(10 mg·kg -1 ) and low level (50 mg·kg -1 ) of the same compound ( P <0.01).There was no difference between the fluorouracil and the low dosage of nolatrexed ( P > 0.05). CONCLUSION: The antiproliferative effect of nolatrexed in vivo and in vitro on cancer cell line and normal cell was selective. The anticancer effect of the compound on the mice with SRS-82 ascitic type of carcinoma or solid tumor was obvious.

关 键 词：抗肿瘤药 肿瘤 实验性 细胞 培养的 洛拉曲克 

分 类 号：R979.1[医药卫生—药品] R965[医药卫生—药学]