Downregulation of MDR1 gene by cepharanthine hydrochloride is related to the activation of c-Jun/JNK in K562/ADR cells.

Abstract

The purpose of the study was to determine the signal transduction mechanism of cepharanthine hydrochloride (CH) on reversing tumor multidrug resistance. RT-PCR and Western blot analysis were used to determine the effects of CH on the expression of MDR1 mRNA and P-glycoprotein in K562/ADR cells when CH was used alone and combined with SP600125, a JNK inhibitor, to explore the effects of CH on JNK pathway. Western blot analysis was used to determine the effects of CH on c-Jun protein expression and phosphorylation, to explore the regulating effects of CH on c-Jun and phosphorylated c-Jun (p-c-Jun) proteins. Our results showed that the inhibitory effect of CH on MDR1 mRNA increased with the concentrations of CH (5.0, 10.0, and 20.0 μM) and the inhibitory effects of CH on MDR1 mRNA and P-glycoprotein increased with the incubation time of CH (0, 12, 24, 36, and 48 hours). The inhibitory effect was weakened after CH combined with SP600125. The expressions of c-Jun and p-c-Jun proteins increased with the incubation time of CH (0, 6, 12, and 24 hours). These findings suggest that CH downregulated the expressions of MDR1 mRNA and P-glycoprotein in a time and concentration manner; the mechanism may be mediated via activating c-Jun/JNK pathway.

• Authors: Li Han, Yafeng Wang, Xiaojuan Guo, Yubing Zhou, Jingmin Zhang, Ning Wang, Jinhua Jiang, Fang Ma, Qingduan Wang
• Journal: BioMed research international (Biomed Res Int) Vol. 2014 Pg. 164391 ( 2014) ISSN: 2314-6141 [Electronic] United States
• PMID: 25386557 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Retracted Publication)

Chemical References

• ABCB1 protein, human
• ATP Binding Cassette Transporter, Subfamily B
• Benzylisoquinolines
• RNA, Messenger
• cepharanthine
• JNK Mitogen-Activated Protein Kinases

Topics

• ATP Binding Cassette Transporter, Subfamily B (biosynthesis, genetics)
• Benzylisoquinolines (administration & dosage)
• Cell Line, Tumor
• Drug Resistance, Multiple (drug effects)
• Drug Resistance, Neoplasm (drug effects)
• Gene Expression Regulation, Neoplastic (drug effects)
• Humans
• JNK Mitogen-Activated Protein Kinases (biosynthesis, genetics)
• K562 Cells
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive (drug therapy, genetics, pathology)
• RNA, Messenger (biosynthesis)
• Signal Transduction (drug effects)