Downregulation of MDR1 gene by cepharanthine hydrochloride is related to the activation of c-Jun/JNK in K562/ADR cells.
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.
Zhang Zhongjing College of Chinese Medicine, Nanyang Institute of Technology, China.
Li
L
Han
School of Pharmaceutical Sciences, Zhengzhou University, China.
Yafeng
Y
Wang
Zhang Zhongjing College of Chinese Medicine, Nanyang Institute of Technology, China.
Xiaojuan
X
Guo
Department of Pharmacy, First Affiliated Hospital of Zhengzhou University, China.
Yubing
Y
Zhou
School of Pharmaceutical Sciences, Zhengzhou University, China ; Henan Academy of Medical and Pharmaceutical Sciences, Zhengzhou University, Zhengzhou Henan 450052, China.
Jingmin
J
Zhang
Henan Academy of Medical and Pharmaceutical Sciences, Zhengzhou University, Zhengzhou Henan 450052, China.
Ning
N
Wang
Henan Academy of Medical and Pharmaceutical Sciences, Zhengzhou University, Zhengzhou Henan 450052, China.
Jinhua
J
Jiang
Henan Academy of Medical and Pharmaceutical Sciences, Zhengzhou University, Zhengzhou Henan 450052, China.
Fang
F
Ma
Henan Academy of Medical and Pharmaceutical Sciences, Zhengzhou University, Zhengzhou Henan 450052, China.
Qingduan
Q
Wang
D018435:ATP Binding Cassette Transporter, Subfamily B / Q000096:biosynthesis* / Q000235:genetics; D044182:Benzylisoquinolines / Q000008:administration & dosage; D045744:Cell Line, Tumor; D018432:Drug Resistance, Multiple / Q000187:drug effects*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000096:biosynthesis / Q000235:genetics*; D020014:K562 Cells; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D012333:RNA, Messenger / Q000096:biosynthesis; D015398:Signal Transduction / Q000187:drug effects; D052117:Benzodioxoles
D018435:ATP Binding Cassette Transporter, Subfamily B; D044182:Benzylisoquinolines; D048031:JNK Mitogen-Activated Protein Kinases; D012333:RNA, Messenger; C513055:ABCB1 protein, human; C006947:cepharanthine; D052117:Benzodioxoles