Mechanism of synergistic anti-tumor effect of PH II -7 with doxorubicin on multi-drug resistant HL-60/ADR cells.
- Author:
Yan-Jun ZHANG
1
;
Rui WANG
;
Xiao-Feng SHAO
;
Dong-Mei FAN
;
Yuan-Fu XU
;
Yuan ZHOU
;
Fang LIU
;
Ye SU
;
Dong-Sheng XIONG
Author Information
- Publication Type:Journal Article
- MeSH: ATP-Binding Cassette, Sub-Family B, Member 1; genetics; metabolism; Doxorubicin; pharmacology; Drug Resistance, Multiple; drug effects; Drug Resistance, Neoplasm; drug effects; Drug Synergism; HL-60 Cells; Humans
- From: Chinese Journal of Hematology 2008;29(9):599-602
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo study the synergistic mechanism between PH II -7 and doxorubicin against multi-drug resistant HL-60/ADR cells and its parent HL-60 cells.
METHODSThe anti-tumor activity of doxorubicin alone and combined with PH II -7 were measured by MTT assay. RNA was extracted from the cells treated with PH II -7 for different times or doses then the expression of MRP gene was measured by RT-PCR. Confocal laser scanning microscopy and FACS were used to detect the intracellular cumulation of doxorubicin in PH II -7 treated HL-60 and HL-60/ADR cells.
RESULTSPH II -7 has anti-tumor effect with IC50 of (0.83 +/- 0.08) micromol/L and (1.74 +/- 0.56) micromol/L for HL-60 and HL-60/ADR, respectively. It could potentiate the anti-tumor effect of doxorubicin with CDI of 0.7 and 0.43 for HL-60 and HL-60/ADR, respectively. PH II -7 and doxorubicin act synergistically in inhibiting the proliferation of HL-60 and HL-60/ADR cells and down-regulating the expression of MRP gene in a dose and time dependent manner. PH II -7 restored the intracellular cumulation of doxorubicin in HL-60/ADR cells to 55% of that in HL-60 cells.
CONCLUSIONPH II -7 can significantly hasten the cytotoxicity of doxorubicin to HL-60 and HL-60/ADR cells through down-regulating the expression of MRP. The synergistic effect was more obvious in HL-60/ADR cells.
