Deguelin regulates nuclear pore complex proteins Nup98 and Nup88 in U937 cells in vitro^1  

作　　者：Hong-li LIU Yan CHEN Guo-hui CUI Qiu-ling WU Jing HE Wei-hua CHEN Jian-feng ZHOU 

机构地区：[1]Department of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022 [2]Department of Hematology Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030,China

出　　处：《Acta Pharmacologica Sinica》2005年第10期1265-1273,共9页中国药理学报（英文版）

基　　金：Project supported by the National Natural Science Foundation of China (№ 30472267)

摘　　要：Aim： To investigate the anticancer effects and the molecular mechanisms of deguelin on human U937 leukemia cells, and to explore the underlying mechanism regulating nucleoporin 98 （Nup98） and nucleoporin 88 （Nup88） in vitro. Methods： The effects of deguelin on the growth of U937 cells were studied by MTT assay. The effect of deguelin on the cell cycle of U937 cells was studied by using a propidium iodide method. The localization of the nuclear pore complex proteins Nup98 and Nup88 was investigated by using immunofluorescence and immunoelectron microscopy. The expression of Nup98 and Nup88 in U937 cells was investigated by using flow cytometry and Western blot. Results： The proliferation of U937 cells was inhibited in the deguelin-treated group, with a 24-h IC50 value of 21,61 nmol/L and a 36-h IC50 value of 17.07 nmol/L. U937 cells treated with deguelin had reduced percentages of cells in the G0/G1 phase, whereas cells accumulated in the S and Gz/M phases. Nup88 and Nup98 were found on both the nuclear and cytoplasmic sides of the U937 cells by using immunofluorescence and immunoelectron microscopy. The expression of Nup98 was upregulated and that of the Nup88 protein was downregulated in U937 cells treated with deguelin. Conclusion： Deguelin is able to inhibit the proliferation of U937 cells by regulating the cell cycle such that cells are arrested at the S and G2/M phases, so that the proportion of cells in the G0/G1 phase decreases. The antitumor effects of deguelin are related to upregulating the expression of Nup98 and downregulating the ex- pression of Nup88 protein in U937 cells.Aim： To investigate the anticancer effects and the molecular mechanisms of deguelin on human U937 leukemia cells, and to explore the underlying mechanism regulating nucleoporin 98 （Nup98） and nucleoporin 88 （Nup88） in vitro. Methods： The effects of deguelin on the growth of U937 cells were studied by MTT assay. The effect of deguelin on the cell cycle of U937 cells was studied by using a propidium iodide method. The localization of the nuclear pore complex proteins Nup98 and Nup88 was investigated by using immunofluorescence and immunoelectron microscopy. The expression of Nup98 and Nup88 in U937 cells was investigated by using flow cytometry and Western blot. Results： The proliferation of U937 cells was inhibited in the deguelin-treated group, with a 24-h IC50 value of 21,61 nmol/L and a 36-h IC50 value of 17.07 nmol/L. U937 cells treated with deguelin had reduced percentages of cells in the G0/G1 phase, whereas cells accumulated in the S and Gz/M phases. Nup88 and Nup98 were found on both the nuclear and cytoplasmic sides of the U937 cells by using immunofluorescence and immunoelectron microscopy. The expression of Nup98 was upregulated and that of the Nup88 protein was downregulated in U937 cells treated with deguelin. Conclusion： Deguelin is able to inhibit the proliferation of U937 cells by regulating the cell cycle such that cells are arrested at the S and G2/M phases, so that the proportion of cells in the G0/G1 phase decreases. The antitumor effects of deguelin are related to upregulating the expression of Nup98 and downregulating the ex- pression of Nup88 protein in U937 cells.

关 键 词：DEGUELIN U937 cells NUCLEOPORIN Nup98 NUP88 

分 类 号：R979.14[医药卫生—药品]