title: Exosomes play an important role in the process of psoralen reverse multidrug resistance of breast cancer.
abstract: Release of exosomes have been shown to play critical roles in drug resistance by delivering cargo. Targeting the transfer of exosomes from resistant cells to sensitive cells may be an approach to overcome some cases of drug resistance.
  
  
  
  In this study, we investigated the potential role of exosomes in the process of psoralen reverse multidrug resistance of MCF-7/ADR cells. Exosomes were isolated by differential centrifugation of culture media from MCF-7/ADR cells (ADR/exo) and MCF-7 parental cells (S/exo). Exosomes were characterized by morphology, exosomal markers and size distribution. The ability of ADR/exo to transfer multidrug resistance was assessed by MTT and real-time quantitative PCR. The different formation and secretion of exosomes were detected by immunofluorescence and transmission electron microscopy. Then we performed comparative transcriptomic analysis using RNA-Seq technology and real-time quantitative PCR to better understand the gene expression regulation in exosmes formation and release after psoralen treatment.
  
  
  
  Our data showed that exosomes derived from MCF-7/ADR cells were able to promote active sequestration of drugs and could induce a drug resistance phenotype by transferring drug-resistance-related gene MDR-1 and P-glycoprotein protein. Psoralen could reduce the formation and secretion of exosomes to overcome drug resistance. There were 21 differentially expressed genes. Gene ontology (GO) pathway analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that the most significantly expressed genes were linked to PPAR and P53 signaling pathways which were related to exosomes formation, secretion and cargo sorting.
  
  
  
  Psoralen can affect the exosomes and induce the reduction of resistance transmission via exosomes might through PPAR and P53 signaling pathways, which might provide a novel strategy for breast cancer resistance to chemotherapy in the future.
authors.affiliation: Department of Thyroid and Breast Surgery, The Affiliated Hospital of Binzhou Medical University, 522 Yellow Three Road, Binzhou, Shandong, 256603, People's Republic of China.
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Thyroid and Breast Surgery, The Affiliated Hospital of Binzhou Medical University, 522 Yellow Three Road, Binzhou, Shandong, 256603, People's Republic of China.
authors.forename: Chengfeng
authors.initials: C
authors.lastname: Xu
authors.affiliation: Department of Thyroid and Breast Surgery, The Affiliated Hospital of Binzhou Medical University, 522 Yellow Three Road, Binzhou, Shandong, 256603, People's Republic of China.
authors.forename: Yitong
authors.initials: Y
authors.lastname: Hua
authors.affiliation: Department of Nneurosurgery, The Affiliated Hospital of Binzhou Medical University, Binzhou, Shandong, 256603, People's Republic of China.
authors.forename: Leitao
authors.initials: L
authors.lastname: Sun
authors.affiliation: Department of Thyroid and Breast Surgery, The Affiliated Hospital of Binzhou Medical University, 522 Yellow Three Road, Binzhou, Shandong, 256603, People's Republic of China.
authors.forename: Kai
authors.initials: K
authors.lastname: Cheng
authors.affiliation: Department of Thyroid and Breast Surgery, The Affiliated Hospital of Binzhou Medical University, 522 Yellow Three Road, Binzhou, Shandong, 256603, People's Republic of China.
authors.forename: Zhongming
authors.initials: Z
authors.lastname: Jia
authors.affiliation: Department of Thyroid and Breast Surgery, The Affiliated Hospital of Binzhou Medical University, 522 Yellow Three Road, Binzhou, Shandong, 256603, People's Republic of China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Han
authors.affiliation: Department of Thyroid and Breast Surgery, The Affiliated Hospital of Binzhou Medical University, 522 Yellow Three Road, Binzhou, Shandong, 256603, People's Republic of China.
authors.forename: Jianli
authors.initials: J
authors.lastname: Dong
authors.affiliation: Department of Thyroid and Breast Surgery, The Affiliated Hospital of Binzhou Medical University, 522 Yellow Three Road, Binzhou, Shandong, 256603, People's Republic of China.
authors.forename: Yuzhen
authors.initials: Y
authors.lastname: Cui
authors.affiliation: Department of Thyroid and Breast Surgery, The Affiliated Hospital of Binzhou Medical University, 522 Yellow Three Road, Binzhou, Shandong, 256603, People's Republic of China. ikb0607@163.com.
authors.forename: Zhenlin
authors.initials: Z
authors.lastname: Yang
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000235:genetics / Q000378:metabolism; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D055354:Exosomes / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D005363:Ficusin / Q000494:pharmacology*; D020869:Gene Expression Profiling; D053263:Gene Regulatory Networks; D006801:Humans; D061986:MCF-7 Cells; D047492:Peroxisome Proliferator-Activated Receptors / Q000235:genetics; D017423:Sequence Analysis, RNA; D016159:Tumor Suppressor Protein p53 / Q000235:genetics
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D047492:Peroxisome Proliferator-Activated Receptors; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D005363:Ficusin
keywords: Breast cancer; Chemoresistance; Exosome; Psoralen