文章基本信息

标题：L1EPO, a Novel Podophyllotoxin Derivative Overcomes P-Glycoprotein-Mediated Multidrug Resistance in K562/A02 Cell Line
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作者：Hong Chen ; Jing Wang ; Jingze Zhang 等
期刊名称：Biological and Pharmaceutical Bulletin
印刷版ISSN：0918-6158
电子版ISSN：1347-5215
出版年度：2009
卷号：32
期号：4
页码：609-613
DOI：10.1248/bpb.32.609
出版社：The Pharmaceutical Society of Japan
摘要：The ineffectiveness of anticancer drugs is frequently observed in cancer chemotherapy. The resistance of tumor cells to various cytotoxic drugs is defined as multidrug resistance (MDR). The purpose of our present study was to investigate the inhibitory effects of L1EPO synthesized by our group on P-glycoprotein (P-gp)-mediated MDR in K562/A02 and KBv200 cell lines, which expressed high levels of P-gp. Both the cytotoxicity of the compound and its ability to inhibit K562/A02 and KBv200 cells were determined by sulforhodamine B sodium salt (SRB) assay. Morphologic apoptosis was detected by Hoechst33342 staining assay. Reverse transcriptase-polymerase chain reaction (RT-PCR) was used to detect mdr-1 gene transcription, and Western blot assay was used to assess P-gp expression. Interestingly, we found that the K562/A02 cell line was rendered resistant toward Adriamycin but not towards L1EPO when compared with the parental cells. Furthermore, L1EPO could down-regulate the mdr-1 gene, and it reduced the expression of P-gp and displayed a perfect dose dependence. Moreover, it had less cytotoxicity in normal human cell lines (fibroblast, VEC), GI₅₀>10 μmol/l. Consequently, L1EPO has the potential to overcome P-glycoprotein-mediated MDR in the K562/A02 cell line.
关键词：L1EPO;Podophyllotoxin;derivative;multidrug resistance;P-glycoprotein