标题：Ligustrazine derivate DLJ14 reduces multidrug resistance of K562/A02 cells by modulating GSTpi activity.
作者：Song YN;Guo XL;Zheng BB;Liu XY;Dong X;Yu LG;Cheng YN
作者机构：[Song, Y.-N] Department of Pharmacology, School of Pharmaceutical Sciences, Shandong University, Jinan 250012, China;[ Guo, X.-L] Department of Pharma 更多
通讯作者地址：[Guo, XL]Shandong Univ, Dept Pharmacol, Sch Pharmaceut Sci, 44 Wen Hua Xi Rd, Jinan 250012, Peoples R China.
来源：Toxicology in vitro: an international journal published in association with BIBRA
关键词：Ligustrazine derivate; Glutathione S-transferase pi (GST pi); Multidrug; resistance (MDR); c-Jun NH(2)-terminal kinase (JNK)
摘要：Multidrug resistance (MDR) of tumor cells is a major obstacle in chemotherapeutic cancer treatment. Over-expression of glutathione S-transferase pi (GSTpi) is one of the mechanisms contributing to MDR. In this study, we investigated the reversal of MDR by DLJ14, a ligustrazine derivate, in adriamycin (Adr) resistant human myelogenous leukemia (K562/A02) cells by modulating the expression of GSTpi and the activity of GST-related enzymes. In the MTT test, DLJ14 showed a weak inhibition on proliferation of both K562/A02 and K562 cells, while verapamil at the same concentration showed a much stronger inhibition. The sensitivity of K562/A02 cells to cytotoxic killing by Adr was enhanced by incubation with DLJ14 as a result of the increased intracellular accumulation of Adr. The accumulation of Adr induced by DLJ14 may due to down regulation of GST-related enzyme activity. Western blot analysis and RT-PCR showed that DLJ14 was able to inhibit the protein expression and mRNA expression of GSTpi in K562/A02 cells. Moreover, DLJ14 increased the expression of cellular c-Jun NH(2)-terminal kinase (JNK) in K562/A02 cells exposure to Adr. This is consistent with the inhibition of GSTpi. These results demonstrate that DLJ14 may be an attractive new agent for the chemosensitization of cancer cells.