title: [The inhibitory effects of dexamethasone on cisplatin induced apoptosis of human lung adenocarcinoma cell SPC-A1 and its molecular mechanism].
abstract: The aim of this study is to investigate the apoptotic inhibition and its molecular mechanism of dexamethasone (DEX) acting on cisplatin (CDDP)-induced apoptosis of human lung adenocarcinoma cell SPC-A1; SPC-A1 cells were pre-cultured in vitro for 24 hours with DEX in different concentrations and then CDDP was added in different concentrations for culturing for further 48 hours. The survival rates of the cells were determined by MTT. The expression of serum/glucocorticoid-induced kinase (SGK-1) and mitogen-activated protein kinase phosphatase-1 (MKP-1) in SPC-A1 cells after being cultured by 1 micromol/l DEX at different time was detected by semi-quantitative RT-PCR technology. The expression of glucocorticoid receptor (GR) in SPC-A1 cells was measured by immunohistochemistry (IHC) with biotin-labeled anti-GR. The results of MTT showed that SPC-A1 cells had resistance to CDDP-induced apoptosis with pre-cultured DEX and the resistance intensity presented DEX concentration-dependent. The expressing quantity of SGK-1 in SPC-A1 cells stimulated by DEX could be elevated and increased with intention of time, but the express of MKP-1 was not detected. Up-regulated expression of GR in SPC-A1 cells stimulated by DEX was detected by IHC. The number of cells expressing GR in SPC-A1 cells was significantly higher than that in the control group. The results showed that DEX inhibited apoptosis of SPC-A1 cells induced by CDDP. The possible molecular mechanism is that elevated expression of GR induced by DEX up-regulates the expression of SGK-1 which locates at the downstream of anti-apoptosis pathway. The apoptosis resistance of SPC-A1 cells may account for all above the factors.
authors.forename: Fei
authors.initials: F
authors.lastname: Cao
authors.forename: Zhihui
authors.initials: Z
authors.lastname: Zhang
mesh_terms: D000230:Adenocarcinoma / Q000473:pathology*; D000077192:Adenocarcinoma of Lung; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology*; D003907:Dexamethasone / Q000494:pharmacology*; D054638:Dual Specificity Phosphatase 1 / Q000378:metabolism; D006801:Humans; D017874:Immediate-Early Proteins / Q000378:metabolism; D008175:Lung Neoplasms / Q000473:pathology*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011965:Receptors, Glucocorticoid / Q000378:metabolism; D015854:Up-Regulation; D000099184:Serum-Glucocorticoid Regulated Kinases
chemical_list: D002945:Cisplatin; D003907:Dexamethasone; D054638:Dual Specificity Phosphatase 1; D017874:Immediate-Early Proteins; D017346:Protein Serine-Threonine Kinases; D011965:Receptors, Glucocorticoid; D000099184:Serum-Glucocorticoid Regulated Kinases; C517019:DUSP1 protein, human