title: Zinc ribbon domain-containing 1 (ZNRD1) mediates multidrug resistance of leukemia cells through regulation of P-glycoprotein and Bcl-2.
abstract: 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.
authors.affiliation: State Key Laboratory of Cancer Biology and Institute of Digestive Diseases, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, Shaanxi, China.
authors.forename: Liu
authors.initials: L
authors.lastname: Hong
authors.forename: Ying
authors.initials: Y
authors.lastname: Piao
authors.forename: Yu
authors.initials: Y
authors.lastname: Han
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.forename: Xiaoyin
authors.initials: X
authors.lastname: Zhang
authors.forename: Yulei
authors.initials: Y
authors.lastname: Du
authors.forename: Shanshan
authors.initials: S
authors.lastname: Cao
authors.forename: Taidong
authors.initials: T
authors.lastname: Qiao
authors.forename: Zhen
authors.initials: Z
authors.lastname: Chen
authors.forename: Daiming
authors.initials: D
authors.lastname: Fan
mesh_terms: 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
chemical_list: 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