[NF-kappaB regulating expression of mdr1 gene and P-gp to reverse drug-resistance in leukemic cells].
This study was purposed to investigate whether the mdr1 participates in antiapoptotic mechanisms of hematologic malignant cells regulated by NF-kappaB and to explore the reversal effect of inhibiting NF-kappaB on drug-resistance of hematologic malignant cells so as to search a novel way for treatment of refractory leukemia. NF-kappaB activity and P-gp expression in K562/A02 cells cultured with PDTC in different concentration or different time were detected by immunohistochemistry and computerized picture analysis. The mdr1 was detected by reverse transcription-polymerase chain reaction, and the relationship among NF-kappaB, P-gp and mdr1 was analyzed. The results showed that in K562/A02 cells the expression of P-gp and mdr1 were positively correlated with NF-kappaB/p65, which showed the concentration and time dependent manner. It is concluded the mechanism of NF-kappaB regulating anti-apoptosis in K562/A02 cells has the correlation with the expression of mdr1 and P-gp. The expression of mdr 1 mRNA and P-gp can be reduced through inhibiting NF-kappaB in K562/A02 cells, so that the sensitivity of chemical therapy can be enhanced on hematologic malignant cells.
Wang
Yi
Y
Department of Hematology, The First Affiliated Hospital, Xi'an Jiaotong University, Xi'an 710061, China.
Liu
Xin
X
Zhang
Hai-Tao
HT
Yu
Min
M
Wang
Hui
H
D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D004317:Doxorubicin / Q000494:pharmacology; D018432:Drug Resistance, Multiple / Q000187:drug effects*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D020014:K562 Cells; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011759:Pyrrolidines / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D013859:Thiocarbamates / Q000494:pharmacology
C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D016328:NF-kappa B; D011759:Pyrrolidines; D012333:RNA, Messenger; D013859:Thiocarbamates; C020972:pyrrolidine dithiocarbamic acid; D004317:Doxorubicin