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标题：Cancerous multi-drug resistance is reduced by Leptomycin B treatment in CCRF-CEM/Taxol cellsCancerous multi-drug resistance is reduced by Leptomycin B treatment in CCRF-CEM/Taxol cells
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作者：Jin-Wu Zhu ; Yong-Xiang Zhang ; Yong-Biao Guan 等
期刊名称：Health
印刷版ISSN：1949-4998
电子版ISSN：1949-5005
出版年度：2012
卷号：4
期号：10
页码：845-855
DOI：10.4236/health.2012.410130
出版社：Scientific Research Publishing
摘要：Objectives: Multi-drug resistance (MDR) to chemotherapy remains a major obstacle to overcome in the successful treatment of patients with cancers. It was recently discovered that Leptomycin B (LMB) reduces the paclitaxel-induced MDR in CCRF-CEM/Taxol cells. However, the mechanism remains unclear. Here we sought to explore the mechanism of LMB to reduce the MDR induced by paclitaxel. Results: LMB has remarkable cytotoxic effects in both sensitive CCRF-CEM and resistant CCRF-CEM/Taxol cell lines. The paclitaxel-induced MDR was reduced by 0.013 μm of LMB. Lower concentration of LMB regulated cell cycle progress, in situ expressions of P-gp, MRP1, and LRP, expression of CRM1, and localization of P-gp and CRM1 in CCRF-CEM/taxol cells. Study Design: Cytotoxicity of LMB on cancerous cell lines was determined by MTT assay. Cell cycle progress and in situ expressions of P-gp, MRP1, and LRP were analyzed by flow cytometry. Expression of CRM1 in the cells was examined by Western blot. And co-localization between P-gp and CRM1 was determined by laser confocal microscopy. Conclusion: The paclitaxel-induced MDR of CCRFCEM/Taxol cells was reduced by lower concentration of LMB. The mechanisms might be related to decreasing in situ expression of drug transporter proteins, promoting cell cycle progress, and altering co-localization between P-gp and CRM1 in the resistant cells.
关键词：Leptomycin B; CCRF-CEM; Multi-Drug Resistance; CRM1; Paclitaxel