【摘 要】
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Background: Multidrug resistance (MDR) is a major impediment to the overall success of chemotherapy in clinical oncology.Recently, the intercellular transfer of ABCB1 between tumor cells has been prop
【机 构】
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Sun Yat-sen University Cancer Center;State Key Laboratory of Oncology in South China;Collaborative I
【出 处】
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2014医学科学前沿暨第三届个体化治疗与抗肿瘤药物研究新趋向研讨会
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Background: Multidrug resistance (MDR) is a major impediment to the overall success of chemotherapy in clinical oncology.Recently, the intercellular transfer of ABCB1 between tumor cells has been proposed to be a novel way to spread drug resistance.Methods: Confocal microscopy and flow cytometry were used for confirmation of intercellular transfer of ABCB1.Microparticles (Mps) were isolated from the culture medium of drug-resistant KBv200 cells by ultra-centrifuge.Function of transferred ABCB1 was determined by MTT and drug accumulation assay.Results: In this study, it was evidenced that ABCB1 could functionally transfer from the resistant donor cells to sensitive recipient cells, thereby resulting in increased resistant phenotype.Importantly, it was found for the first time that a short-time stimulus of chemotherapeutical drugs could boost the intercellular transfer of ABCB1,but no inducible expression.Moreover, chemotherapeutical drugs Dox significantly increased Mps secreted by drug-resistant cells (KBv200), which were reported to serve as vectors in the intercellular transfer of ABCB1, and effectively stimulated this Mps-mediated intercellular transfer of ABCB1.Conclusion: These findings reveal a novel mechanism of transient cellular self-protection against exposure to chemotherapeutical drugs, that is intercellular ABCB1 transfer resulting in the increase of cellular overall resistance.So it has important implications for interpreting the link between chemotherapy and acquired.
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