Investigation on inhibitory effect of folic acid on methotrexate-induced epithelial-mesenchymal transition focusing  on dihydrofolate reductase.

In this study, the role of dihydrofolate reductase (DHFR), a target of MTX, in FA-mediated inhibition of MTX-induced EMT was evaluated. The inhibitory effects of FA and tetrahydrofolate (THF), a metabolite of FA produced by DHFR, on MTX-induced increases in mRNA expression of α-SMA, an EMT marker, were compared. The IC50 values of FA and THF for DHFR were 103.3 and 19.4 μM, respectively. In contrast, DHFR knockdown did not alter the mRNA expression of α-SMA. Notably, the inhibitory effect of FA, but not THF, on MTX-induced EMT was blunted in DHFR knockdown cells. These results suggested that DHFR may not directly contribute to MTX-induced EMT, but may contribute to suppression of MTX-induced EMT via production of THF in A549 cells. PMID: 31601464 [PubMed - as supplied by publisher]
Source: Drug Metabolism and Pharmacokinetics - Category: Drugs & Pharmacology Tags: Drug Metab Pharmacokinet Source Type: research