Involvement of MAPK Phosphatase-1 in Dexamethasone-Induced Chemoresistance in Lung Cancer
Involvement of MAPK Phosphatase-1 in Dexamethasone-Induced Chemoresistance in Lung Cancer
复制标题
MAPK磷酸酶1参与地塞米松诱导的肺癌化疗耐药
DOI：
10.1179/joc.2011.23.4.221
复制
发表时间：
2011-08-01
影响因子：
1.8
通讯作者：
Zhang, Chengwen
中科院分区：
文献类型：
--
作者：
Huang, Jian;Wang, Haibo;Zhang, Chengwen
Dexamethasone (DEX) has been frequently used as a co-medication in cytotoxic cancer therapy, mostly for supportive care in alleviating the acute toxic effects on healthy tissues. Although recent studies have demonstrated DEX-induced resistance to cytotoxic treatment in several solid tumors, no specific molecular mechanism of action has been reported. Here, we assessed the effect of DEX on the cisplatin-induced cytotoxicity in fresh surgically resected specimens from Chinese patients with lung cancer. We also examined the effects of DEX and cisplatin on the apoptotic signaling pathway in the well-established human lung adenocarcinoma cell line A549. Our results show that DEX treatment inhibits cisplatin-induced cell apoptosis by up-regulation of cellular mitogen-activated protein kinase phosphatase-1 (MKP-1) and subsequent deactivation of p38 protein kinase. Knock down of MKP-1 by RNA interference reversed the DEX-induced inhibition of cisplatin-induced cell a poptosis. These data suggest that administration of DEX during the clinical therapy of Chinese lung cancer patients must be carefully considered, and indicate that MKP-1 and p38 protein kinase are potential targets for DEX-induced drug resistance.
