Effect of the NHE-1-specific inhibitor DMA on pHi, proliferation and apoptosis of HL-60/ADM cells in vitro.
- Author:
Cheng CHANG
1
;
Pei-Yan KONG
;
Xing-Hua CHEN
;
Xian-Gui PENG
;
Lin LIU
;
Hong LIU
;
Dong-Feng ZENG
;
Xue LIANG
;
Qing-Yu WANG
Author Information
1. Department of Hematology, Xinqiao Hospital, The Third Military Medical University, Chongqing 400037, China.
- Publication Type:Journal Article
- MeSH:
Amiloride;
analogs & derivatives;
pharmacology;
Apoptosis;
drug effects;
Cell Cycle;
drug effects;
Cell Proliferation;
drug effects;
Doxorubicin;
pharmacology;
Drug Resistance, Neoplasm;
HL-60 Cells;
Humans;
Hydrogen-Ion Concentration;
Sodium-Hydrogen Exchangers;
antagonists & inhibitors
- From:
Journal of Experimental Hematology
2006;14(3):488-491
- CountryChina
- Language:Chinese
-
Abstract:
The aim of this study was to evaluate the effect of dimethyl amiloride (DMA), a specific inhibitor of Na(+)/H(+) exchanger-1 (NHE-1), on intracellular pH value (pHi), proliferation and apoptosis of HL-60/ADM cells in vitro. After treatment with DMA at different doses, pHi of HL-60 and HL-60/ADM cell lines were determined by using pH-sensitive fluorescence dye BECEF-AM; the rate of growth inhibition of cells was detected with MTT assay; cell cycle was detected by flow cytometric DNA analysis; cell apoptosis was observed with terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL). The results showed that pHi in HL-60/ADM cells was higher than that in HL-60 cells. After treatment with DMA at different doses, pHi decreased, the rate of growth inhibition and the rate of apoptotic cells in HL-60/ADM cells were all higher than those in HL-60 cells. Meanwhile, after treatment with DMA during 100 micromol/L to 150 micromol/L, the increase amplitude of G(0)/G(1) phase cells and the decrease amplitude of S + G(2)/M cells in HL-60/ADM cells were higher than those in HL-60 cells. It is concluded that by causing intracellular acidification, the NHE-1-specific inhibitor DMA inhibits proliferation of HL-60/ADM cells and induces apoptosis of HL-60/ADM cells, and the degree of this growth inhibition of HL-60/ADM cells is higher than that of HL-60 cells.
