A novel mechanism of transient cellular self-protection against chemotherapeutical drugs via stimula

来源 :广东省生物物理学会2013年学术研讨会 | 被引量 : 0次 | 上传用户:shanshan0000
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  ABCB1 (P-gp/MDR1/ABCB1),one of the most important mediator of multidrug resistance (MDR),has been observed as a result of the selective pressure from chemotherapy and is associated with poor clinical outcome.Previous work has found that individual cells communicate with each other by exchanging the contents of their membrane protein ABCB1.However,the study to investigate whether the transfers of ABCB1 are stimulated by the presence of chemotherapeutical drugs has not yet been reported.In this study,we provided strong evidence for the existence of the functional ABCB1 transfers from drug-resistant cells to sensitive cells.Importantly,it was found for the first time that a short-time stimulus of chemotherapeutical drugs could concentration-dependently boost the intercellular transfer of ABCB1,but no inducible expression.Moreover,chemotherapeutical drugs doxorubicine (Dox) significantly increased micropaticles (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.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 multicellular overall resistance.So it has important implications for interpreting the link between chemotherapy and acquired MDR.
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