Cinnamaldehyde Treatment of Prostate Cancer-Associated Fibroblasts Prevents Their Inhibitory Effect on T Cells Through Toll-Like Receptor 4

Drug Design, Development and Therapy

关键词: cinnamaldehyde;    cancer-associated fibroblasts;    prostate cancer;    tlr4;   

DOI  :  

来源: DOAJ

【 摘 要 】

Jie Mei,1– 3,* Jing Ma,2,4,5,* Yuwei Xu,4 Yuanyuan Wang,6 Minghua Hu,6 Fangli Ma,6 Zhihai Qin,1,2,4 Rui Xue,1 Ning Tao2 1Medical Research Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, People’s Republic of China; 2Key Laboratory of Protein and Peptide Pharmaceuticals, Institute of Biophysics, Chinese Academy of Sciences, Beijing, People’s Republic of China; 3College of Life Science & Technology, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 4College of Life Science, University of the Chinese Academy of Sciences, Beijing, People’s Republic of China; 5School of Basic Medical Sciences of Southwest Medical University, Luzhou, People’s Republic of China; 6Infinitus Chinese Herbal Immunity Research Center, Infinitus China Company Ltd, Guangzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zhihai Qin; Ning TaoKey Laboratory of Protein and Peptide Pharmaceuticals, Institute of Biophysics, Chinese Academy of Sciences, No. 15 Datun Road, Chaoyang Area, Beijing City, People’s Republic of ChinaEmail [e-mail] [e-mail]: Cancer-associated fibroblasts (CAFs) promote tumor progression; thus, drugs that can modify CAFs need to be identified.Methods: To test the effect of cinnamaldehyde on prostate CAFs, the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl-2H-tetrazolium bromide assay was used to determine their survival. When spleen cells were treated with CAF supernatant, the proliferation of T cells was inhibited as determined by flow cytometry. After cinnamaldehyde treatment, this immunosuppressive function of CAFs was partially reversed. To explore the molecular mechanism, Western blotting and the quantitative real-time polymerase chain reaction were applied, and TLR4-dependent signaling pathway-related protein and mRNA levels were quantified.Results: Cinnamaldehyde acted on the TLR4-dependent signaling pathway, altering the function of CAFs such that its supernatant no longer inhibited the proliferation of T cells.Conclusion: These data indicate that cinnamaldehyde can modify the functions of CAFs, which may be helpful for treating tumors. Cinnamaldehyde can suppress CAF T-cell inhibition.Keywords: cinnamaldehyde, cancer-associated fibroblasts, prostate cancer, TLR4

【 授权许可】

Unknown