Yi Ying-Jie, Jia Xiu-Hong, Zhu Cong, Wang Jian-Yong, Chen Jie-Ru, Wang Hong, Li You-Jie
Department of Pediatrics, The Affiliated Hospital of Binzhou Medical University, Binzhou, Shandong 256603, P.R. China.
Department of Biochemistry and Molecular Biology, Key Laboratory of Tumor Molecular Biology, Binzhou Medical University, Yantai, Shandong 264003, P.R. China.
Oncol Lett. 2018 Jun;15(6):10070-10076. doi: 10.3892/ol.2018.8563. Epub 2018 Apr 25.
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 (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.
白血病细胞中的多药耐药性（MDR）是化疗治疗的主要障碍。多药耐药蛋白1（MRP1）的高表达和组成性激活与多种肿瘤类型中抗癌药物耐药性的发展有关。c-Jun氨基末端激酶1（JNK1）的活性与MDR的发生和MRP1的表达有关。本研究旨在探讨茄碱使耐阿霉素（ADR）的人髓性白血病细胞系K562/ADM对ADR重新敏感的能力。细胞计数试剂盒-8检测结果表明，茄碱抑制K562/ADM细胞增殖。用茄碱处理后，K562/ADM细胞对ADR的敏感性增加，表现为细胞内ADR积累增加。蛋白质印迹法表明，用茄碱处理导致MRP1蛋白表达降低，提示茄碱诱导的ADR积累是由于MRP1表达下调所致。观察到茄碱介导的MRP1下调依赖于JNK信号通路。总之，本研究结果表明，茄碱可逆转K562/ADM细胞中的MDR，可能是治疗人类髓性白血病的一种新型治疗药物。
