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INHIBITORY EFFECTS OF MIFEPRISTONE ON THE GROWTH OF HUMAN GASTRIC CANCER CELL LINE MKN-45 IN VITRO AND IN VIVO 被引量:4
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作者 da-qiangli Li-huaPan Zhi-minShao 《Chinese Medical Sciences Journal》 CAS CSCD 2004年第4期237-242,共6页
Objective To explore the effects of mifepristone on the growth of human gastric cancer cell line MKN-45 and its possible mechanisms. Methods In situ hybridization was used to detect the expression of progesterone rece... Objective To explore the effects of mifepristone on the growth of human gastric cancer cell line MKN-45 and its possible mechanisms. Methods In situ hybridization was used to detect the expression of progesterone receptor (PR) mRNA in MKN-45 cells. Proliferation, cell cycle distribution, and the expression of Bcl-xL and vascular endothelial growth factor (VEGF) of MKN-45 cells incubated with various concentrations of mifepristone (1, 5, 10, and 20 μmol/L) were analyzed using MTT reduction assay, flow cytometry, reverse transcription-polymerase chain reaction (RT-PCR), and enzyme-linked immunoab-sorbent assay (ELISA), respectively. After transplantation of MKN-45 cells underneath the skin of athymic mice, mifepristone was administrated with the dose of 50 mg/(kg·d) for 6 weeks to evaluate the tumor growth. Apoptosis and the expression of proliferating cell nuclear antigen (PCNA) in xenografted tumors were detected using transmission electron microscopy and immunohistochemical staining, respectively. Results PR mRNA was highly expressed in cultured MKN-45 cell. Mifepristone dose-dependently inhibited the pr-oliferation of MKN-45 cells, and the inhibitory rate was dramatically increased from 7.21% to 47.23%. The inhibitory effect was accompanied by a dose-dependent increase in the percentage of cells in G 0 /G 1 phase, and with a concurrent decrease in the proportion of S- and G 2 /M-phase cells and the proliferative index from 57.65% to 24.54%. Meanwhile, mifepristone down-regulated the expression of Bcl-xL and VEGF in a dose-dependent manner. In vivo, mifepristone effectively inhibited the growth of xenografted tumors in nude mice (55.14% for inhibitory rate), induced apoptosis, and down-regulated PCNA expression in gastric cancer. Conclusion Mifepristone exerts significant growth inhibitory effects on PR-positive human MKN-45 gastric cancer cells via multiple mechanisms, and may be a beneficial agent against the tumor. 展开更多
关键词 MIFEPRISTONE gastric neOplasm PROLIFERATION
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