Involvement of NF-κB in the response of embryonic cells to Methotrexate

The involvement of NF-κB in the regulation of the apoptotic process was demonstrated previously, however, its exact role has not been established yet. In order to unravel mechanisms underlying teratogen-induced cell death, we tried in our present study to assess the involvement of the p65 subunit of NF-κB in the response of mouse embryonic fibroblasts (MEFs) to the anti-cancer drug Methotrexate (MTX), using p65 knockout MEFs (p65−/−). Indeed, this cell line was found to be more susceptible to the exposure to MTX, demonstrated by more profound changes in cell survival, cell cycle, proliferation and the percentage of apoptotic or necrotic cells, as compared to wild type (WT) MEFs. Also, a different pattern of intracellular localization of p65 in WT cells as well as IκBα and Bax in both cell lines was detected in response to MTX. Altogether, our results implicate the p65 subunit of NF-κB to play an important role in the response of embryonic cells to MTX.