盐酸洛拉曲克在体内、外对S-180细胞株的抗增殖作用

Antiproliferative Effect of Nolatrexed Dihydrochloride on Cell Line S-180 in vitro and in vivo

研究全合成新型胸苷合成酶抑制剂盐酸洛拉曲克在体内、外对S 1 80细胞株及正常人胚肾HEK2 93细胞的抗增殖作用 ;使用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盐酸洛拉曲克对S 1 80所致肿瘤的治疗作用 .结果表明 :在体外盐酸洛拉曲克对S 1 80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 5 ) ;体内实验显示盐酸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 ,疗效与氟尿嘧啶 ( 1 0mg kg)相当 (P >0 .0 5 )或更好 (P <0 .0 5 ) .可见 ,盐酸洛拉曲克在体内、外对S 1 80肿瘤细胞有显著的抗增殖作用 。

The anticancer effect of nolatrexed dihydrochloride on mouse cancer cell line S-180 in vitro and in vivo and the antiproliferative effect on normal human embryo kidney cell HEK293 were studied.The inhibition rate of the compound on the cultured cancer cell line S-180 and human embryo kidney cell HEK293 were assayed by MTT method. Antineoplasm effect on the mice with S-180 ascitic type of carcinoma and solid tumor were evaluated by survival time escalation and the weight reduction of the tumor tissue respectively. Result:The antiproliferative effect of nolatrexed dihydrochloride on cancer cell and normal cell were selective in vitro. The inhibitory potency of the compound on cancer cell S-180 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 nolatrexed dihydrochloride and fluorouracil (10?mg/kg) comparing to that of the untreated mice (P<0.01). The mean survival time of high (100?mg/kg) and moderate (75?mg/kg) dosage of nolatrexed dihydrochloride treated groups were much longer than that of fluorouracil treated group (P<0.05).So the antiproliferative effect of nolatrexed dihydrochloride on cancer cell line and normal cell was selective in vitro; the anticancer effect of nolatrexed dihydrochloride on the mice with S-180 ascitic type of carcinoma or solid tumor was obvious.