Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.5.1.3 (dihydrofolate reductase)
 5,819 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID:Effect of methotrexate on the growth and human chorionic gonadotropin secretion of human choriocarcinoma cell lines in vitro. 668 28

The sensitivity to methotrexate (MTX) and mechanisms of the drug resistance of seven kinds of human choriocarcinoma cell lines were studied in vitro. The results were as follows. Each cell line of HCCM-5 , BeWo, IMa, and NUC-1 secreted more than 200ng/10(6) cells/48 hours of human chorionic gonadotropin (hCG), whereas GCH-1, ENAMI-1, and SCH secreted less than 20ng/10(6) cells/48 hours. HCCM-5 cell line was the most sensitive to MTX judging from the inhibition of both 3H-thymidine uptake and cell growth in vitro. Each cell line of BeWo, IMa, and NUC-1 revealed sensitivity to 2 X 10(-8)M MTX, but such cell lines as GCH-1, ENAMI-1, and SCH showed resistance to MTX. The cell lines which revealed sensitivity to MTX incorporated more 3H-MTX and showed less intracellular dihydrofolate reductase activity than resistant cell lines.
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PMID:[MTX sensitivity and the mechanism of resistance of various choriocarcinoma cells in culture]. 668 70