Effect of methotrexate on the growth and human chorionic gonadotropin secretion of human choriocarcinoma cell lines in vitro.
The effect of methotrexate (MTX) on the growth and human chorionic gonadotropin (hCG) secretion of five gestational and two nongestational human choriocarcinoma cell lines was studied in vitro. A striking heterogeneity in hCG secretion was noted among the cell lines. The growth of cells which secreted large quantities of hCG, such as HCCM-5, BeWo, and IMa, was inhibited by continuous exposure to 2 X 10(-8)M MTX. In contrast, cells which secreted little hCG, such as SCH, ENAMI-1, and GCH-1, showed no response to the growth inhibitory action of 2 X 10(-8)M MTX and the 3H-thymidine uptake was not reduced by treatment with MTX at doses of up to 10(-4)M for 48 hours. The common morphologic alterations observed in the cells which responded to MTX were an increase in the number of multinucleated giant cells, the appearance of vacuoles and granules in the cytoplasm, and enlargement of the nuclei. Increased hCG secretion was observed in accordance with the appearance of such morphologically altered cells. Part of the mechanisms of resistance to MTX appeared to involve both impairment of MTX uptake by the cells and an increase in the level of intracellular dihydrofolate reductase.
D002460:Cell Line; D002822:Choriocarcinoma / Q000378:metabolism* / Q000473:pathology; D006063:Chorionic Gonadotropin / Q000032:analysis / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008727:Methotrexate / Q000494:pharmacology*; D011247:Pregnancy; D011863:Radioimmunoassay; D013762:Tetrahydrofolate Dehydrogenase / Q000032:analysis; D014594:Uterine Neoplasms / Q000378:metabolism* / Q000473:pathology
D006063:Chorionic Gonadotropin; D013762:Tetrahydrofolate Dehydrogenase; D008727:Methotrexate