Kang Qingwei, Yan Shu
Pharmacy Department, Tianjin Nankai Hospital, Tianjin 300100, P.R. China.
Exp Ther Med. 2015 Apr;9(4):1345-1350. doi: 10.3892/etm.2015.2254. Epub 2015 Feb 3.
Drug resistance is an important obstacle to human leukemia therapeutics. Piperlongumine has previously demonstrated the ability to suppress certain human tumor processes; however, the ability of piperlongumine to reverse the drug resistance of human leukemia and its mechanism of action have not yet been clearly elucidated. In this study, the doxorubicin resistance reversal effect of piperlongumine on K562/A02 human leukemia cells and the underlying mechanism were investigated. The results indicated that piperlongumine promoted doxorubicin sensitivity, apoptosis, the intracellular accumulation of rhodamine-123, the activities of caspase-3 and -8, and the expression of reactive oxygen species, p53, p27 and p-PTEN. Furthermore, it suppressed the expression of P-glycoprotein, MDR1, MRP1, survivin and p-Akt, and the transcriptional activities of NF-κB and twist, and arrested the cell cycle in the G2/M phase. The results indicate that piperlongumine has the potential to be used as a therapeutic agent for human leukemia.
耐药性是人类白血病治疗的一个重要障碍。胡椒碱先前已证明具有抑制某些人类肿瘤进程的能力；然而，胡椒碱逆转人类白血病耐药性的能力及其作用机制尚未明确阐明。在本研究中，研究了胡椒碱对K562/A02人白血病细胞的阿霉素耐药逆转作用及其潜在机制。结果表明，胡椒碱可促进阿霉素敏感性、细胞凋亡、罗丹明-123的细胞内积累、caspase-3和-8的活性以及活性氧、p53、p27和p-PTEN的表达。此外，它还抑制P-糖蛋白、MDR1、MRP1、生存素和p-Akt的表达，以及NF-κB和twist的转录活性，并使细胞周期停滞在G2/M期。结果表明，胡椒碱有潜力用作人类白血病的治疗药物。
