化疗药物促进外泌体介导的ABCB1细胞间转移作用及其机制

肿瘤化疗失败的主要原因在于其迅速获得多药耐药性（MDR），其机理不明。新近，我们发现传统化疗药物可促进ABCB1从高表达ABCB1的细胞瞬时转移至无ABCB1表达的细胞介导其MDR，外泌体（Exosomes）可能是其转移载体，但其转移规律、影响因素及调控机制均不清楚。本研究拟利用绿色荧光蛋白GFP、细胞膜标记探针DiI 等标记技术，以共聚焦显微镜、流式细胞术等深入研究化疗药物促进ABCB1 膜间转移的作用及转移的ABCB1功能，揭示化疗药物促进ABCB1 细胞间转移的规律；从外泌体的产生、分泌调控、内吞途径及再循环等方面研究化疗药物促进ABCB1 细胞间转移的分子机制，为解释肿瘤细胞“瞬时”获得“暂时”对化疗药物耐药，逃避化疗杀伤提出一种新理论；鉴定参与ABCB1细胞间转移的关键蛋白或伴侣分子并阐明其作用机制，为预防与克服MDR 提供新思路和新策略。

Ｍultidurg resistance (MDR) is the major cause of chemotherapy failure. Recently, we found that ABCB1 can be transferred from ABCB1-overexpressing cancer cells to ABCB1-negative recipient cells at the presence of conventional chemotherapeutic agents, resulting in a rapid resistance to chemotherapeutical agents in recipient cells. Exosomes may be act as the carrier. But the mechanisms of intercellular transfer of ABCB1 are poorly understood. To investigate the factors and regularity of the intercellular transfer of ABCB1, the ABCB1 transfer will be imaged by confocal microscopy and determined by flow cytometry at the presence or absence of various factors. The molecular mechanism by which chemotherapeutic drugs promote ABCB1 transferring to recipient cells will be investigated, including the biogenesis, secretion, endocytosis and recycle of exosomes. This study will propose a novel theory to explain why cancer cells can promptly evade chemotherapy. Also, it will provide new potential target or strategy for overcoming MDR mediated by ABCB1 to achieve a better therapeutic effect.