Zinc ribbon domain-containing 1 (ZNRD1) mediates multidrug resistance of leukemia cells through regulation of P-glycoprotein and Bcl-2.
Here, we investigated the role of zinc ribbon domain-containing 1 (ZNRD1) in multidrug resistance (MDR) of leukemia cells and the possible underlying mechanisms. ZNRD1 was found overexpressed in the vincristine-induced MDR leukemia cell HL-60/vincristine moreso than its parental cell HL-60. Up-regulation of ZNRD1 expression could confer resistance of both P-glycoprotein (P-gp)-related and P-gp-nonrelated drugs on HL-60 cells and suppress Adriamycin-induced apoptosis accompanied by decreased accumulation and increased releasing amount of Adriamycin. ZNRD1 could significantly up-regulate the expression of P-gp, Bcl-2, and the transcription of the MDR1 gene but not alter the expression of MDR-associated protein, glutathione S-transferase activity, or intracellular glutathione content in leukemia cells. In addition, inhibition of ZNRD1 expression by RNA interference or P-gp inhibitor could partially reverse ZNRD1-mediated MDR. The further study of the biological functions of ZNRD1 may be helpful for understanding the mechanisms of MDR of leukemia and developing possible strategies to treat leukemia.
Hong
Liu
L
State Key Laboratory of Cancer Biology and Institute of Digestive Diseases, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, Shaanxi, China.
Piao
Ying
Y
Han
Yu
Y
Wang
Jun
J
Zhang
Xiaoyin
X
Du
Yulei
Y
Cao
Shanshan
S
Qiao
Taidong
T
Chen
Zhen
Z
Fan
Daiming
D
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000502:physiology*; D017209:Apoptosis / Q000502:physiology; D001483:Base Sequence; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000502:physiology*; D004317:Doxorubicin / Q000378:metabolism; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D005978:Glutathione / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D018922:HL-60 Cells; D006801:Humans; D007938:Leukemia / Q000201:enzymology / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014700:Verapamil / Q000494:pharmacology
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D017931:DNA Primers; D004268:DNA-Binding Proteins; C406241:POLR1H protein, human; D019253:Proto-Oncogene Proteins c-bcl-2; D004317:Doxorubicin; D014700:Verapamil; D005982:Glutathione Transferase; D005978:Glutathione