The relationship between p38MAPK and apoptosis during paclitaxel resistance of ovarian cancer cells |
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Authors: | Lu Meisong Xiao Lan Li Zhimin and Hu Jianli |
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Institution: | (1) Department of Gynecology and Obstetrics, the First Affiliated Hospital of Harbin Medical University, Harbin, 150001, China;(2) Department of Gynecology and Obstetrics, the Third Affiliated Hospital of Sun Yan-sen University, Guangzhou, 510630, China;(3) Department of Gynecology and Obstetrics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China;(4) The Cancer Center of Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430023, China |
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Abstract: | Summary 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 on the apoptosis of A2780/Taxol cells, a drug-resistant human ovarian carcinoma cell line. p38MAPK
protein expression in SB203580-treated cells was immunochemically measured. The 50% inhibition concentration (IC50) of paclitaxel on A2780/Taxol cells was determined by MTT assay. MDR-1 mRNA, and expression of p38MAPK and phospho-p53 protein
were detected by RT-PCR and Western blotting, respectively. The apoptosis rate of A2780/Taxol cells was (19.7±1.04)% 24 h
after SB203580 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 paclitaxel was (57.18±2.01)%. As compared with the control group
and the untreated group, p38MAPK protein and MDR-1 mRNA in SB203580-treated cells was substantially decreased. The expression
of p53 protein was significantly increased. It is concluded that p38MAPK pathway is related to paclitaxel resistance of ovarian
carcinoma, and blockade of this pathway can promote the apoptosis of the drug-resistant cells and reverse the drug-resistance.
Moreover, p38MAPK-mediated apoptosis in paclitaxel-resistant ovarian carcinoma cells depends on the activation of p53.
This project was supported by a grant from R&D program of Heilongjiang Province (No. GB05C402-11). |
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Keywords: | ovarian carcinoma cell apoptosis p38 mitogen-activated protein kinase multidrug resistance |
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