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肉桂醛通过激活Toll样受体4(TLR4)诱导髓源性抑制细胞凋亡。

Cinnamaldehyde causes apoptosis of myeloid-derived suppressor cells through the activation of TLR4.

作者信息

He Wanzhuo, Zhang Wensheng, Zheng Qilin, Wei Zheng, Wang Yuanyuan, Hu Minghua, Ma Fangli, Tao Ning, Luo Cong

机构信息

College of Life Sciences, Peking University, Beijing 100871, P.R. China.

Key Laboratory of Protein and Peptide Pharmaceuticals, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, P.R. China.

出版信息

Oncol Lett. 2019 Sep;18(3):2420-2426. doi: 10.3892/ol.2019.10544. Epub 2019 Jun 28.

Abstract

Malignant tumors are among the most life-threatening diseases in the world. Although many different types of antitumor agents are available, severe side effects and toxicity limit their applications. Myeloid-derived suppressor cells (MDSCs) inhibit the antitumor immune response by suppressing the proliferation of T cells, the production of cytokines and the killing of tumor cells. As MDSCs have become novel targets in cancer therapy, this research focused on the anti-MDSC function of cinnamaldehyde (CA), which is extracted from cinnamon, a traditional Chinese spice. In the present study, MDSCs isolated from the spleens of mice with colon cancer were used as an model to assess the efficacy of CA. Treatment of MDSCs with CA significantly decreased cell proliferation and induced apoptotic cell death. Subsequent experiments demonstrated that CA treatment enhanced the expression of Bax and caspase-9 and inhibited the expression of Bcl-2, suggesting that CA induced apoptosis in the MDSCs via the intrinsic pathway. Taken together, the results demonstrated that CA exhibited significant anti-MDSC activity and attenuated the suppression of the antitumor immune response, indicating a potential use for CA in cancer therapy.

摘要

恶性肿瘤是世界上最危及生命的疾病之一。尽管有许多不同类型的抗肿瘤药物,但严重的副作用和毒性限制了它们的应用。髓源性抑制细胞(MDSCs)通过抑制T细胞增殖、细胞因子产生和肿瘤细胞杀伤来抑制抗肿瘤免疫反应。由于MDSCs已成为癌症治疗的新靶点,本研究聚焦于从传统中国香料肉桂中提取的肉桂醛(CA)的抗MDSC功能。在本研究中,从患有结肠癌的小鼠脾脏中分离出的MDSCs用作评估CA疗效的模型。用CA处理MDSCs可显著降低细胞增殖并诱导凋亡性细胞死亡。随后的实验表明,CA处理增强了Bax和caspase-9的表达并抑制了Bcl-2的表达,表明CA通过内源性途径诱导MDSCs凋亡。综上所述,结果表明CA表现出显著的抗MDSC活性并减弱了对抗肿瘤免疫反应的抑制,表明CA在癌症治疗中具有潜在用途。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c83c/6676727/40c0d8f28844/ol-18-03-2420-g00.jpg

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