Molecular mechanism of reversing multi-drug resistance of K562/AO2 by puerarin.
- Author:
Jin-wei CHEN
1
;
Shi TAO
;
Rong LUO
;
Guang-sen ZHANG
;
Yun-xiao XU
Author Information
1. Department of Hematology, Second Xiangya Hospital, Central South University, Changsha 410007, China. jinwei73104@yahoo.com.cn
- Publication Type:Journal Article
- MeSH:
ATP Binding Cassette Transporter, Subfamily B;
biosynthesis;
genetics;
Antineoplastic Agents, Phytogenic;
pharmacology;
Drug Resistance, Multiple;
drug effects;
genetics;
Drug Resistance, Neoplasm;
drug effects;
genetics;
Humans;
Inhibitor of Apoptosis Proteins;
Isoflavones;
pharmacology;
K562 Cells;
Microtubule-Associated Proteins;
biosynthesis;
genetics;
NF-kappa B;
metabolism;
Survivin
- From:
Journal of Central South University(Medical Sciences)
2008;33(3):216-221
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:To determine the molecular mechanism of reversing multi-drug resistance of K562/AO2 by puerarin.
METHODS:Effects of ADR and puerarin on NF-kappaB activity of K562,K562/AO2 were tested by immunofluorescence. The expression of survivin of K562,K562/AO2 was examined by immunocytochemistry. The p-gp expression was detected by flow cytometry.
RESULTS:The NF-kappaB activity of K562 was significantly higher than that of K562/AO2. The NF-kappaB activity of K562 treated by ADR was significantly higher than untreated. The NF-kappaB activity of K562 which was pretreated by puerarin and then treated by ADR was much lower than that treated by ADR alone. The NF-kappaB activity of K562/AO2 intervened by puerarin was lower than that unintervened by puerarin.The p-gp and survivin expression of K562/AO2 was significantly higher than K562. The p-gp and survivin expression of K562 treated by ADR was higher than that untreated by ADR. But the p-gp and survivin expression of K562 which was pretreated by puerarin and then treated by ADR was much lower than that not pretreated by puerarin.The p-gp and survivin expression of K562/AO2 intervened by puerarin was lower than that unintervened by puerarin. The expression was negatively correlated to the duration of intervention. The inhibition effect demonstrated time dependence.
CONCLUSION:The activation of NF-kappaB can increase the expression of p-gp and survivin, which may be part of the molecular mechanism of multi-drug resistance of K562. Puerarin can prevent and stop the multi-drug resistance in K562 and reverse the multi-drug resistance of K562/AO2 to ADR by inhibiting the activity of NF-kappaB and the expression of p-gp and survivin.
