Mechanisms of preventive effect of tetrandrine on acquired multidrug resistance in K562 cells.
- Author:
Xiao-Lan ZHU
1
;
Wen-Lin XU
;
Xu-Jing LÜ
;
Wen-Juan LUO
;
Lei-Lei ZHOU
;
Qiao-Yun CHEN
Author Information
1. Department of Hematology, Jiangsu University, Zhenjiang, Jiangsu Province, China.
- Publication Type:Journal Article
- MeSH:
ATP-Binding Cassette, Sub-Family B, Member 1;
metabolism;
Apoptosis;
drug effects;
genetics;
Benzylisoquinolines;
pharmacology;
Drug Resistance, Multiple;
drug effects;
genetics;
Drug Resistance, Neoplasm;
drug effects;
genetics;
Humans;
Inhibitor of Apoptosis Proteins;
metabolism;
K562 Cells;
Proto-Oncogene Proteins c-jun;
metabolism;
Y-Box-Binding Protein 1;
metabolism
- From:
Journal of Experimental Hematology
2011;19(2):363-366
- CountryChina
- Language:Chinese
-
Abstract:
This study was purposed to explore the mechanisms of preventive effect of tetrandrine (TTD) on doxorubicin (ADM)-induced multidrug resistance (MDR) in human leukemia cell line K562 from two aspects of the transcription control of MDR1 gene and cell apoptosis. The experiment was divided into 3 groups: group I-blank control; group II-ADM-induced drug-resistance; group III-ADM-induced drug-resistance after pretreatment with TTD. Reverse transcription-PCR (RT-PCR) was used to detect the mRNA expression levels of c-Jun, YB-1 and Survivin genes. Western blot was used to determine the nuclear protein expression levels of c-Jun and YB-1. Flow cytometry was used to assay the apoptosis of cells. The results showed that as compared with group I, the expression levels of c-Jun mRNA and nuclear protein decreased (p < 0.05), as well as the expression levels of YB-1 mRNA and nuclear protein increased in group II (p < 0.05). However, the expression of Survivin mRNA had no change (p > 0.05); the apoptosis rate of cells was 8.31%. As compared with group II, the expression levels of c-Jun mRNA and nuclear protein increased (p < 0.05), expression levels of YB-1 mRNA and nuclear protein as well as Survivin mRNA decreased in group III (p < 0.05). The apoptosis of cells was 97.2%. It is concluded that TTD can inhibit the expression of YB-1 and up-regulate the expression of c-Jun, thus inhibit the expression of MDR1 gene. TTD can also inhibit the expression of Survivin and increase the apoptosis of cells induced by ADM.
