Quercetin exerts anti-tumor immune mechanism by regulating IL-6/JAK2/ STAT3 signaling pathway to deplete Treg cells

被引:7
|
作者
Liao, Yupei [1 ]
Xie, Xiaoqing [1 ]
Zhang, Chu [1 ]
Zhong, Haijing [1 ]
Shan, Luchen [1 ]
Yu, Pei [1 ]
Xu, Lipeng [1 ]
机构
[1] Jinan Univ, Inst New Drug Res,State Key Lab Bioact Mol & Drugg, Coll Pharm,Int Cooperat Lab Tradit Chinese Med Mod, Guangzhou Key Lab Innovat Chem Drug Res Cardiocere, Guangzhou 510632, Peoples R China
基金
中国国家自然科学基金;
关键词
Quercetin; Breast cancer; Treg; IL-6/JAK2/STAT3; Anti-tumor immune; T-CELLS; CANCER; INDUCTION; NK;
D O I
10.1016/j.toxicon.2024.107747
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Breast cancer is still the leading cause of death among women worldwide. Due to the lack of effective drug targets, triple-negative breast cancer has a worse prognosis and higher mortality compared with other types of breast cancer, and chemotherapy is still the main treatment for triple-negative breast cancer at present. Quercetin (QUE) is a flavonoid compound found in a variety of fruits and vegetables. The mechanism of QUE has been extensively studied, such as prostate cancer, colon cancer, ovarian cancer, etc. However, the anti -tumor immune mechanism of QUE in triple-negative breast cancer remains unclear. Therefore, we assessed the anti -tumor immune effects of QUE on triple-negative breast cancer using both 4T1 cells and a xenograft mouse model of 4T1 cells. In vitro, we examined the inhibitory effects of QUE on 4T1 cells and its molecular mechanisms through MTT, Transwell, ELISA, and Western blotting. In vivo, by establishing a xenograft mouse model, we utilized flow cytometry, immunohistochemistry, ELISA, and Western blotting to evaluate the anti -tumor immune effects of QUE on triple-negative breast cancer. The results indicate that QUE inhibits the proliferation, migration, and invasion of 4T1 cells, concurrently significantly suppressing the IL-6/JAK2/STAT3 signaling pathway. Furthermore, it depletes Treg cell content in 4T1 xenograft mice, thereby improving the tumor immune microenvironment and promoting the cytotoxicity of relevant tumor immune cells. These findings suggest that QUE may serve as a potential adjuvant for immune therapy in triple-negative breast cancer.
引用
收藏
页数:14
相关论文
共 50 条
  • [1] The role of IL-6/JAK2/STAT3 signaling pathway in cancers
    Huang, Bei
    Lang, Xiaoling
    Li, Xihong
    FRONTIERS IN ONCOLOGY, 2022, 12
  • [2] Quercetin shows anti-tumor effect in hepatocellular carcinoma LM3 cells by abrogating JAK2/STAT3 signaling pathway
    Wu, Liwei
    Li, Jingjing
    Liu, Tong
    Li, Sainan
    Feng, Jiao
    Yu, Qiang
    Zhang, Jie
    Chen, Jiaojiao
    Zhou, Yuting
    Ji, Jie
    Chen, Kan
    Mao, Yuqing
    Wang, Fan
    Dai, Weiqi
    Fan, Xiaoming
    Wu, Jianye
    Guo, Chuanyong
    CANCER MEDICINE, 2019, 8 (10): : 4806 - 4820
  • [3] Quercetin Induces Apoptosis in Glioblastoma Cells by Suppressing Axl/IL-6/STAT3 Signaling Pathway
    Kim, Hyo In
    Lee, Sol Ji
    Choi, Yu-Jeong
    Kim, Min Jeong
    Kim, Tai Young
    Ko, Seong-Gyu
    AMERICAN JOURNAL OF CHINESE MEDICINE, 2021, 49 (03): : 767 - 784
  • [4] Inhibition of the JAK2/STAT3 signaling pathway exerts a therapeutic effect on osteosarcoma
    Yan, Jun
    Wang, Qianliang
    Zou, Kang
    Wang, Li
    Schwartz, Eric B.
    Fuchs, James R.
    Zheng, Zugen
    Wu, Jianqiang
    MOLECULAR MEDICINE REPORTS, 2015, 12 (01) : 498 - 502
  • [5] IL-6 mediated JAK/STAT3 signaling pathway in cancer patients with cachexia
    Eskiler, Guney G.
    Bezdegumeli, E.
    Ozman, Z.
    Ozkan, Deveci A.
    Bilir, C.
    Kucukakca, B. N.
    Ince, M. N.
    Men, A. Y.
    Aktas, O.
    Horoz, Y. E.
    Akpinar, D.
    Genc, I
    Kaleli, S.
    BRATISLAVA MEDICAL JOURNAL-BRATISLAVSKE LEKARSKE LISTY, 2019, 120 (11): : 819 - 826
  • [6] Study on expression of IL-6/JAK/STAT3 signaling pathway in category IIIB prostatitis
    Li, Guangyu
    Lan, Haiyan
    Liang, Jihong
    Xian, Jing
    Fang, Dan
    Mo, Yuncong
    Zheng, Cheng
    Dong, Yingjin
    Li, Yuanfa
    INTERNATIONAL JOURNAL OF CLINICAL AND EXPERIMENTAL MEDICINE, 2018, 11 (04): : 3779 - 3785
  • [7] IL-17 induces AKT-dependent IL-6/JAK2/STAT3 activation and tumor progression in hepatocellular carcinoma
    Gu, Fang-Ming
    Li, Quan-Lin
    Gao, Qiang
    Jiang, Jia-Hao
    Zhu, Kai
    Huang, Xiao-Yong
    Pan, Jin-Feng
    Yan, Jun
    Hu, Jin-Hui
    Wang, Zheng
    Dai, Zhi
    Fan, Jia
    Zhou, Jian
    MOLECULAR CANCER, 2011, 10
  • [8] Activation of the IL-6/JAK/STAT3 signaling pathway in human middle ear cholesteatoma epithelium
    Liu, Wei
    Xie, Shumin
    Chen, Xing
    Rao, Xingwang
    Ren, Hongmiao
    Hu, Bing
    Yin, Tuanfang
    Xiang, Yuyan
    Ren, Jihao
    INTERNATIONAL JOURNAL OF CLINICAL AND EXPERIMENTAL PATHOLOGY, 2014, 7 (02): : 709 - 715
  • [9] Flavonoids, a prenatal prophylaxis via targeting JAK2/STAT3 signaling to oppose IL-6/MIA associated autism
    Parker-Athill, Ellisa
    Luo, Deyan
    Bailey, Antoinette
    Giunta, Brian
    Tian, Jun
    Shytle, R. Douglas
    Murphy, Tanya
    Legradi, Gabor
    Tan, Jun
    JOURNAL OF NEUROIMMUNOLOGY, 2009, 217 (1-2) : 20 - 27
  • [10] Napabucasin Inhibits Proliferation and Migration of Glioblastoma Cells (U87) by Regulating JAK2/STAT3 Signaling Pathway
    Unlu, Ilker
    Ozdemir, Ilhan
    Tuncer, Mehmet Cudi
    MEDICINA-LITHUANIA, 2024, 60 (10):