Solanine reverses multidrug resistance in human myelogenous leukemia K562/ADM cells by downregulating MRP1 expression

被引:13
作者
Yi, Ying-Jie [1 ]
Jia, Xiu-Hong [1 ]
Zhu, Cong [1 ]
Wang, Jian-Yong [1 ]
Chen, Jie-Ru [1 ]
Wang, Hong [1 ]
Li, You-Jie [2 ]
机构
[1] Binzhou Med Univ, Affiliated Hosp, Dept Pediat, 661 Second Yellow River Rd, Binzhou 256603, Shandong, Peoples R China
[2] Binzhou Med Univ, Dept Biochem & Mol Biol, Key Lab Tumor Mol Biol, Yantai 264003, Shandong, Peoples R China
关键词
multidrug resistance; solanine; reverse; multidrug resistance protein 1; phosphorylated-c-Jun N-terminal kinase 1; N-TERMINAL KINASE; P-GLYCOPROTEIN; NITRIC-OXIDE; HEPG2; CELLS; INHIBITION; GLYCOALKALOIDS; ALPHA; INVOLVEMENT; DOXORUBICIN; APOPTOSIS;
D O I
10.3892/ol.2018.8563
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Multidrug resistance (MDR) in leukemia cells is a major obstacle to chemotherapeutic treatment. High expression and constitutive activation of multidrug resistance protein 1 (MRP1) has been associated with the development of resistance to anticancer drugs in a number of tumor types. The activity of c-Jun N-terminal kinase 1 (JNK1) is associated with the occurrence of MDR and MRP1 expression. The present study aimed to investigate the ability of solanine to resensitize the Adriamycin (R) (ADR)-resistant human myelogenous leukemia cell line K562/ADM to ADR. Results of the Cell Counting Kit-8 assay demonstrated that solanine inhibited K562/ADM cell proliferation. K562/ADM cell sensitivity to ADR was increased following treatment with solanine, indicated by increased intracellular accumulation of ADR. Western blotting demonstrated that treatment with solanine led to reduced MRP1 protein expression, suggesting that solanine-induced ADR accumulation is due to the downregulation of MRP1 expression. Solanine-mediated MRP1 downregulation was observed to be dependent on the JNK signaling pathway. In conclusion, the results of the present study suggest that solanine reverses MDR in K562/ADM cells and may represent a novel therapeutic agent for the treatment of human myelogenous leukemia.
引用
收藏
页码:10070 / 10076
页数:7
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