Dimethyl Sulfoxide Suppresses Mouse 4T1 Breast Cancer Growth by Modulating Tumor-Associated Macrophage Differentiation
Journal of Breast Cancer 2014³â 17±Ç 1È£ p.25 ~ p.32
(Deng Rui) - Sichuan University West China Medical School West China Hospital State Key Laboratory of Biotherapy and Cancer Center
(Wang Shi-Min) - Sichuan University West China Medical School West China Hospital State Key Laboratory of Biotherapy and Cancer Center
(Yin Tao) - Sichuan University West China Medical School West China Hospital State Key Laboratory of Biotherapy and Cancer Center
(Ye Ting-Hong) - Sichuan University West China Medical School West China Hospital State Key Laboratory of Biotherapy and Cancer Center
(Shen Guo-Bo) - Sichuan University West China Medical School West China Hospital State Key Laboratory of Biotherapy and Cancer Center
(Li Ling) - Sichuan University West China Medical School West China Hospital State Key Laboratory of Biotherapy and Cancer Center
(Zhao Jing-Yi) - Sichuan University West China Medical School West China Hospital Department of Medical Oncology
(Sang Ya-Xiong) - Sichuan University West China Medical School West China Hospital State Key Laboratory of Biotherapy and Cancer Center
(Duan Xiao-Gang) - Sichuan University West China Medical School West China Hospital State Key Laboratory of Biotherapy and Cancer Center
(Wei Yu-Quan) - Sichuan University West China Medical School West China Hospital State Key Laboratory of Biotherapy and Cancer Center
Abstract
Purpose: 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.
Conclusion: 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.
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Breast neoplasms, Dimethyl sulfoxide, Macrophage
KMID :
1134120140170010025
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