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

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.