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Cinnamaldehyde Treatment of Prostate Cancer-Associated Fibroblasts Prevents Their Inhibitory Effect on T Cells Through Toll-Like Receptor 4.
Drug Design, Development and Therapy ( IF 4.7 ) Pub Date : 2020-08-18 , DOI: 10.2147/dddt.s241410
Jie Mei 1, 2, 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 Tao 2
Affiliation  

Introduction: 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


中文翻译:

前列腺癌相关成纤维细胞的肉桂醛治疗通过 Toll 样受体 4 防止其对 T 细胞的抑制作用。

简介:癌症相关成纤维细胞(CAFs)促进肿瘤进展;因此,需要确定可以修饰 CAF 的药物。
方法:为了测试肉桂醛对前列腺 CAF 的影响,使用 3-[4,5-二甲基噻唑-2-基]-2,5-二苯基-2H-四唑溴化物测定法确定其存活率。当用 CAF 上清液处理脾细胞时,流式细胞术确定 T 细胞的增殖受到抑制。肉桂醛处理后,CAFs 的这种免疫抑制功能被部分逆转。为探索其分子机制,应用蛋白质印迹法和定量实时聚合酶链反应,对 TLR4 依赖的信号通路相关蛋白和 mRNA 水平进行了定量。
结果:肉桂醛作用于依赖 TLR4 的信号通路,改变 CAF 的功能,使其上清液不再抑制 T 细胞的增殖。
结论:这些数据表明肉桂醛可以改变CAFs的功能,这可能有助于治疗肿瘤。肉桂醛可以抑制 CAF T 细胞的抑制作用。

关键词:肉桂醛,癌相关成纤维细胞,前列腺癌,TLR4
更新日期:2020-08-18
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