To investigate the relationship between the expression of early growth response gene 1 (EGR-1) and p38MAPK pathway in the
paclitaxel resistance of ovarian
carcinoma cells, the effect of p38MAPK inhibitor
SB203580 on cell apoptosis was examined by using
Hoechst 33258 staining. The intracellular Rh123 (
Rhodamine 123) accumulation was detected by the flow cytometry (FCM). The 50% inhibition concentration (IC50) of
paclitaxel for A2780/
Taxol cells was determined by MTT method. Electrophoretic motility shift assay (EMSA) was employed to examine the EGR-1DNA binding activity. MDR1 and EGR-1
mRNA were assessed by RT-PCR. The expressed of p-gp, phosphorylated p53 and p38 were detected by Western blotting.
SB203580 could remarkably promote the apoptosis of A2780/
Taxol cells, and the cell apoptosis was in a time-dependent manner. Cellular Rh123 accumulation was increased, and the IC50 of
paclitaxel for A2780/
Taxol cells was decreased significantly. A2780/
Taxol cell line after
SB203580 treatment was shown to have a significantly higher level of EGR-1
DNA binding activity.
SB203580 down-regulated the activity of p38MAPK pathway, but up-regulated EGR-1 expression.
SB203580 significantly increased the level of cellular phosphorylated p53
protein, but decreased the p-gp
protein level and MDR1
mRNA level in A2780/
Taxol cells. There existed a close relationship between p38MAPK pathway and the
paclitaxel resistance of ovarian
carcinoma cells. The expression of EGR-1 mediated by p38MAPK pathway plays a critical role in
paclitaxel resistance of ovarian
carcinoma cells.