Effects of mifepristone on proliferation of human gastric adenocarcinoma cell line SGC-7901 in vitro.
OBJECTIVE
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-7901 cells. After treatment with various concentrations of mifepristone (2.5, 5, 10, 20 micromol/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-7901 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.


CONCLUSIONS
Mifepristone effectively inhibited the proliferation of PR-positive human gastric adenocarcinoma cell line SGC-7901 in vitro through multiple mechanisms, and may be a beneficial agent against human adenocarcinoma.
State Key Laboratory of Ultrasound Engineering in Medicine, Chongqing Medical University, PO Box 153, Chongqing 400016, China.
Da-Qiang
DQ
Li
Zhi-Biao
ZB
Wang
Jin
J
Bai
Jie
J
Zhao
Yuan
Y
Wang
Kai
K
Hu
Yong-Hong
YH
Du
D000230:Adenocarcinoma; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3; D020169:Caspases / Q000235:genetics; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006727:Hormone Antagonists / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D015735:Mifepristone / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D011980:Receptors, Progesterone / Q000235:genetics; D013274:Stomach Neoplasms; D051020:bcl-X Protein
C494811:BCL2L1 protein, human; D006727:Hormone Antagonists; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D011980:Receptors, Progesterone; D051020:bcl-X Protein; D015735:Mifepristone; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases