A549/DDP derived exosomes can affect cisplatin chemosensitivity via transporting CXCR4 to A549 cells

The resistance of cancer cells to the anti-cancer drugs is the most important reason that affecting the efficacy of the non-small cell lung cancer (NSCLC) chemotherapy; thus, to explore the underlying mechanism of drug resistance of NSCLC medications is urgently needed for improving the therapeutic efficacy of current anti-NSCLC chemotherapies. The aim of the present study is to explore the roles of exosomes in the chemosensitivity of A549 cells and the related mechanism. A549 cells and cisplatin resistant cell line A549/DDP derived exosomes were isolated, and the expressions of CXCR4 were compared. Then, after cisplatin treatment, A549 cells were treated with exosomes, and the proliferation, apoptosis, migration, and invasion of the cells were examined. Finally, the tumorigenic effect of A549/DDP derived exosomes were also evaluated by cisplatin treated xenograft tumor mice models in vivo. We found that A549/DDP derived exosomes increased the proliferation, migration, and invasion, and inhibited the apoptosis and cisplatin sensitivity of A549 cells. CXCR4 was also significantly increased in cells treated with A549/DDP derived exosomes. Furthermore, A549/DDP derived exosomes may also decrease the chemosensitivity of NSCLC cells to cisplatin in vivo. Our data suggested that A549/DDP derived exosomes can affect the chemosensitivity of A549 cells to cisplatin, possibly by transporting CXCR4 to A549 cells. Our data may provide novel evidence for the investigation of drug resistance of NSCLC.