期刊
CELL CYCLE
卷 14, 期 15, 页码 2473-2483出版社
TAYLOR & FRANCIS INC
DOI: 10.1080/15384101.2015.1005530
关键词
drug resistance; exosomes; mesenchymal stem cells; gastric cancer
类别
资金
- Major Research Plan of National Natural Science Foundation of China [91129718]
- National Natural Science Foundation of China [81272481]
- Jiangsu Province's Project of Scientific and Technological Innovation and Achievements Transformation [BL2012055]
- Jiangsu Province for Outstanding Sci-tech Innovation Team in Colleges and Universities [SJK2013-10]
- Jiangsu Province's Outstanding Medical Academic Leader and Sci-tech Innovation Team Program [LJ201117]
- Priority Academic Program Development of Jiangsu Higher Education Institutions
Mesenchymal stem cells (MSCs) play an important role in chemoresistance. Exosomes have been reported to modify cellular phenotype and function by mediating cell-cell communication. In this study, we aimed to investigate whether exosomes derived from MSCs (MSC-exosomes) are involved in mediating the resistance to chemotherapy in gastric cancer and to explore the underlying molecular mechanism. We found that MSC-exosomes significantly induced the resistance of gastric cancer cells to 5-fluorouracil both in vivo and ex vivo. MSC-exosomes antagonized 5-fluorouracil-induced apoptosis and enhanced the expression of multi-drug resistance associated proteins, including MDR, MRP and LRP. Mechanistically, MSC-exosomes triggered the activation of calcium/calmodulin-dependent protein kinases (CaM-Ks) and Raf/MEK/ERK kinase cascade in gastric cancer cells. Blocking the CaM-Ks/Raf/MEK/ERK pathway inhibited the promoting role of MSC-exosomes in chemoresistance. Collectively, MSC-exosomes could induce drug resistance in gastric cancer cells by activating CaM-Ks/Raf/MEK/ERK pathway. Our findings suggest that MSC-exosomes have profound effects on modifying gastric cancer cells in the development of drug resistance. Targeting the interaction between MSC-exosomes and cancer cells may help improve the efficacy of chemotherapy in gastric cancer.
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