title: Dimethyl Sulfoxide Suppresses Mouse 4T1 Breast Cancer Growth by Modulating Tumor-Associated Macrophage Differentiation.
abstract: OBJECTIVE
  The universal organic solvent dimethyl sulfoxide (DMSO) can be used as a differentiation inducer of many cancer cells and has been widely used as a solvent in laboratories. However, its effects on breast cancer cells are not well understood. The aim of this study is to investigate the effect and associated mechanisms of DMSO on mouse breast cancer.
  
  
  METHODS
  We applied DMSO to observe the effect on tumors in a mouse breast cancer model. Tumor-associated macrophages (TAMs) were tested by flow cytometry. Ex vivo tumor microenvironment was imitated by 4T1 cultured cell conditioned medium. Enzyme-linked immunosorbent assays were performed to detect interleukin (IL)-10 and IL-12 expression in medium. To investigate the cytotoxicity of DMSO on TAMs, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays were performed.
  
  
  RESULTS
  We found that DMSO produced tumor retardation when injected into mouse peritoneal cavities in a certain concentration range (0.5-1.0 mg/g). Furthermore, as detected by flow cytometry, TAM subtypes were found to be transformed. We further imitated a tumor microenvironment in vitro by using 4T1 cultured cell conditioned medium. Similarly, by using low concentration DMSO (1.0%-2.0% v/v), TAMs were induced to polarize to the classically activated macrophage (M1-type) and inhibited from polarizing into the alternatively activated macrophage (M2-type) in the conditioned medium. IL-10 expression in tumors was reduced, while IL-12 was increased compared with the control. Furthermore, we reported that 2.0% (v/v) DMSO could lead to cytotoxicity in peritoneal macrophages after 48 hours in MTT assays.
  
  
  CONCLUSIONS
  Our findings suggest that DMSO could exert antitumor effects in 4T1 cancer-bearing mice by reversing TAM orientation and polarization from M2- to M1-type TAMs. These data may provide novel insight into studying breast cancer immunotherapy.
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Deng
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu, China.
authors.forename: Shi-Min
authors.initials: SM
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Yin
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu, China.
authors.forename: Ting-Hong
authors.initials: TH
authors.lastname: Ye
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu, China.
authors.forename: Guo-Bo
authors.initials: GB
authors.lastname: Shen
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Medical Oncology, West China Hospital, West China Medical School, Sichuan University, Chengdu, China.
authors.forename: Jing-Yi
authors.initials: JY
authors.lastname: Zhao
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu, China.
authors.forename: Ya-Xiong
authors.initials: YX
authors.lastname: Sang
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu, China.
authors.forename: Xiao-Gang
authors.initials: XG
authors.lastname: Duan
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu, China.
authors.forename: Yu-Quan
authors.initials: YQ
authors.lastname: Wei
keywords: Breast neoplasms; Dimethyl sulfoxide; Macrophage
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