The Relationship between p38MAPK and Apoptosis during Paclitaxel Resistance of Ovarian Cancer Cells / 华中科技大学学报（医学）（英德文版）

ABSTRACT

To investigate the relationship between p38 mitogen-activated protein kinase (p38MAPK)and cell apoptosis during the paclitaxel resistance of ovarian carcinoma cell lines, flow cytometry(FCM) and PI staining were employed to determine the effect of p38MAPK inhibitor SB203580 onthe apoptosis of A2780/Taxol cells, a drug-resistant human ovarian carcinoma cell line. p38MAPKprotein expression in SB203580-treated cells was immunochemically measured. The 50% inhibitionconcentration (IC<,50) of paclitaxel on A2780/Taxol cells was determined by MTT assay. MDR-1mRNA, and expression of p38MAPK and phospho-p53 protein were detected by RT-PCR and West-ern blotting, respectively. The apoptosis rate of A2780/Taxol cells was (19.7±1.04)% 24 h afterSB203580 treatment. A significant difference in apoptosis rate was found among experiment group,control group and untreated group (P<0.05). The relative reversal rate of A2780/Taxol cells to pacli-taxel was (57.18±2.01)%. As compared with the control group and the untreated group, p38MAPKprotein and MDR-1 mRNA in SB203580-treated cells was substantially decreased. The expression ofp53 protein was significantly increased. It is concluded that p38MAPK pathway is related to pacli-taxel resistance of ovarian carcinoma, and blockade of this pathway can promote the apoptosis of thedrug-resistant cells and reverse the drug-resistance. Moreover, p38MAPK-mediated apoptosis in pa-clitaxel-resistant ovarian carcinoma cells depends on the activation of p53.