[Molecular mechanism of reversing multi-drug resistance of K562/AO2 by puerarin].
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.


CONCLUSIONS
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.
Chen
Jin-wei
JW
Department of Hematology, Second Xiangya Hospital, Central South University, Changsha 410007, China. jinwei73104@yahoo.com.cn
Tao
Shi
S
Luo
Rong
R
Zhang
Guang-sen
GS
Xu
Yun-xiao
YX
D018435:ATP Binding Cassette Transporter, Subfamily B / Q000096:biosynthesis / Q000235:genetics; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D018432:Drug Resistance, Multiple / Q000187:drug effects* / Q000235:genetics; D019008:Drug Resistance, Neoplasm / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D007529:Isoflavones / Q000494:pharmacology*; D020014:K562 Cells; D008869:Microtubule-Associated Proteins / Q000096:biosynthesis / Q000235:genetics; D016328:NF-kappa B / Q000378:metabolism*; D000077022:Survivin
D018435:ATP Binding Cassette Transporter, Subfamily B; D000972:Antineoplastic Agents, Phytogenic; C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D007529:Isoflavones; D008869:Microtubule-Associated Proteins; D016328:NF-kappa B; D000077022:Survivin; C033607:puerarin