Distribution of nolatrexed dihydrochloride in mice bearing S180 sarcoma and its effect on liver cancer cell lines in vitro

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.