title: [Mechanisms of preventive effect of tetrandrine on acquired multidrug resistance in K562 cells].
abstract: This study was purposed to explore the mechanisms of preventive effect of tetrandrine (TTD) on doxorubicin (ADM)-induced multidrug resistance (MDR) in human leukemia cell line K562 from two aspects of the transcription control of MDR1 gene and cell apoptosis. The experiment was divided into 3 groups: group I-blank control; group II-ADM-induced drug-resistance; group III-ADM-induced drug-resistance after pretreatment with TTD. Reverse transcription-PCR (RT-PCR) was used to detect the mRNA expression levels of c-Jun, YB-1 and Survivin genes. Western blot was used to determine the nuclear protein expression levels of c-Jun and YB-1. Flow cytometry was used to assay the apoptosis of cells. The results showed that as compared with group I, the expression levels of c-Jun mRNA and nuclear protein decreased (p < 0.05), as well as the expression levels of YB-1 mRNA and nuclear protein increased in group II (p < 0.05). However, the expression of Survivin mRNA had no change (p > 0.05); the apoptosis rate of cells was 8.31%. As compared with group II, the expression levels of c-Jun mRNA and nuclear protein increased (p < 0.05), expression levels of YB-1 mRNA and nuclear protein as well as Survivin mRNA decreased in group III (p < 0.05). The apoptosis of cells was 97.2%. It is concluded that TTD can inhibit the expression of YB-1 and up-regulate the expression of c-Jun, thus inhibit the expression of MDR1 gene. TTD can also inhibit the expression of Survivin and increase the apoptosis of cells induced by ADM.
authors.affiliation: Department of Hematology, Jiangsu University, Zhenjiang, Jiangsu Province, China.
authors.forename: Xiao-Lan
authors.initials: XL
authors.lastname: Zhu
authors.forename: Wen-Lin
authors.initials: WL
authors.lastname: Xu
authors.forename: Xu-Jing
authors.initials: XJ
authors.lastname: Lü
authors.forename: Wen-Juan
authors.initials: WJ
authors.lastname: Luo
authors.forename: Lei-Lei
authors.initials: LL
authors.lastname: Zhou
authors.forename: Qiao-Yun
authors.initials: QY
authors.lastname: Chen
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D044182:Benzylisoquinolines / 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 / Q000378:metabolism; D020014:K562 Cells; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D000077022:Survivin; D051840:Y-Box-Binding Protein 1 / Q000378:metabolism
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; C107489:BIRC5 protein, human; D044182:Benzylisoquinolines; D051034:Inhibitor of Apoptosis Proteins; D016755:Proto-Oncogene Proteins c-jun; D000077022:Survivin; D051840:Y-Box-Binding Protein 1; C070856:YBX1 protein, human; C009438:tetrandrine