摘要
AIM: To explore the effects of mifepristone, a progesterone receptor (PR) antagonist, on the proliferation of human gastric adenocarcinoma cell line SGC-7 901 in vitro and the possible mechanisms involved.METHODS: In situ hybridization was used to detect the expression of PR mRNA in SGC-7 901 cells. After treatment with various concentrations of mifepristone (2.5, 5, 10,20μmol/L) at various time intervals, the ultrastructural changes, cell proliferation, cell-cycle phase distribution, and the expression of caspase-3 and Bcl-XL were analyzed using transmission electron microscopy (TEM), tetrazolium blue (MTT) assay, ^3H-TdR incorporation, flow cytometry, and reverse transcription-polymerase chain reaction (RT-PCR).RESULTS: Mifepristone markedly induced apoptosis and inhibited cell proliferation of PR- positive SGC-7 901 cells revealed by TEM, MTT assay and ^3H-TdR incorporation, in a dose- and time-dependent manner. The inhibitory rate was increased from 8.98% to 51.29%. Flow cytometric analysis showed mifepristone dose-dependently decreased cells in S and G2/M phases, increased cells in G0/G1 phase,reduced the proliferative index from 57.75% to 22.83%.In addition, mifepristone up-regulated the expression of caspase-3, and down- regulated the Bcl-XL expression,dose-dependently.CONCLUSION: Mifepristone effectively inhibited the proliferation of PR-positive human gastric adenocarcinoma cell line SGC-7 901 in vilrothrough multiple mechanisms, and may be a beneficial agent against human adenocarcinoma.
AIM:To explore the effects of mifepristone,a progesterone receptor (PR) antagonist,on the proliferation of human gastric adenocarcinoma cell line SGC-7 901 in vitro and the possible mechanisms involved. METHODS:In situ hybridization was used to detect the expression of PR mRNA in SGC-7 901 cells.After treatment with various concentrations of mifepristone (2.5,5,10, 20 μmol/L) at various time intervals,the ultrastructural changes,cell proliferation,cell-cycle phase distribution,and the expression of caspase-3 and Bcl-X_L were analyzed using transmission electron microscopy (TEM),tetrazolium blue (MTT) assay,~3H-TdR incorporation,flow cytometry,and reverse transcription-polymerase chain reaction (RT-PCR). RESULTS:Mifepristone markedly induced apoptosis and inhibited cell proliferation of PR- positive SGC-7 901 cells revealed by TEM,MTr assay and ~3H-TdR incorporation,in a dose- and time-dependent manner.The inhibitory rate was increased from 8.98% to 51.29%.Flow cytometric analysis showed mifepristone dose-dependently decreased cells in S and G_2/M phases,increased cells in G_0/G_1 phase, reduced the proliferative index from 57.75% to 22.83%. In addition,mifepristone up-regulated the expression of caspase-3,and down- regulated the Bcl-X_L expression, dose-dependently. CONCLUSION:Mifepristone effectively inhibited the proliferation of PR-positive human gastric adenocarcinoma cell line SGC-7 901 in vitro through multiple mechanisms,and may be a beneficial agent against human adenocarcinoma.
基金
Supported by the National Key Research Project Foundation of China,No.96-905-02-01,and the National Natural Science Foundation of China,No.39630340
