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:Guo, XL
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
出版年:2011
卷:25
期:4
页码:937-943
DOI:10.1016/j.tiv.2011.03.002
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.
收录类别:SCOPUS;SCIE
WOS核心被引频次:9
Scopus被引频次:15
资源类型:期刊论文
原文链接:https://www.scopus.com/inward/record.uri?eid=2-s2.0-79955479186&doi=10.1016%2fj.tiv.2011.03.002&partnerID=40&md5=7c0dcd9b4e07562f1bac4ad304b87404
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