Liu Miao, Tang Rong, Jiang Yi
Department of Paediatrics, Renmin Hospital, Wuhan University, Wuhan, 430060 Hubei People's Republic of China.
Indian J Hematol Blood Transfus. 2017 Dec;33(4):500-508. doi: 10.1007/s12288-017-0808-x. Epub 2017 Mar 30.
This study aims to investigate the effects and mechanism of pantoprazole on multidrug resistant leukemia K562/A02 and K562/ADM cell lines. K562/A02 and K562/ADM cells at logarithmic growth phase were pre-treated with different concentration of pantoprazole (0, 50, 100, 200 μg/mL) for 24 h. Flow cytometry was used to measure the cell growth cycle and apoptosis. RT-PCR and Western blot were used to measure the expression of p-PI3K, p-AKT, p-mTOR, P-glycoprotein (P-gp) and multidrug resistance-associated protein-1 (MRP1). Pantoprazole pretreatment significantly increased the ratio of G0/G1 phase but decreased the S phase of K562/A02 and K562/ADM cells in dose-dependent manner ( < 0.05). Flow cytometry analysis indicated that pretreatment of leukemic cells with pantoprazole induced apoptosis in a dose-dependent manner. RT-PCR and Western blot analysis indicated that pantoprazole pretreatment inhibited the mRNA and protein expression of p-PI3K, p-Akt, p-mTOR, P-gp and MRP1 in K562/A02 and K562/ADM cells in a dose-dependent manner ( < 0.05). Pantoprazole arrested cell cycle and induced apoptosis of multidrug resistant leukemic cells by inhibiting the expression of P-gp and MRP1 through PI3K/Akt/mTOR signaling pathway.
本研究旨在探讨泮托拉唑对多药耐药白血病K562/A02和K562/ADM细胞系的作用及其机制。对数生长期的K562/A02和K562/ADM细胞用不同浓度的泮托拉唑（0、50、100、200μg/mL）预处理24小时。采用流式细胞术检测细胞生长周期和凋亡情况。采用RT-PCR和蛋白质免疫印迹法检测p-PI3K、p-AKT、p-mTOR、P-糖蛋白（P-gp）和多药耐药相关蛋白-1（MRP1）的表达。泮托拉唑预处理可使K562/A02和K562/ADM细胞的G0/G1期比例显著增加，S期比例呈剂量依赖性降低（<0.05）。流式细胞术分析表明，泮托拉唑预处理白血病细胞可呈剂量依赖性诱导细胞凋亡。RT-PCR和蛋白质免疫印迹分析表明，泮托拉唑预处理可呈剂量依赖性抑制K562/A02和K562/ADM细胞中p-PI3K、p-Akt、p-mTOR、P-gp和MRP1的mRNA和蛋白表达（<0.05）。泮托拉唑通过PI3K/Akt/mTOR信号通路抑制P-gp和MRP1的表达，从而阻滞细胞周期并诱导多药耐药白血病细胞凋亡。
