Liraglutide activates nature killer cell-mediated antitumor responses by inhibiting IL-6/STAT3 signaling in hepatocellular carcinoma

Liraglutide activates nature killer cell-mediated antitumor responses by inhibiting IL-6/STAT3 signaling in hepatocellular carcinoma

Inflammatory IL-6/STAT3 signaling is constitutively activated in diverse cancers and is associated with malignant cell proliferation, invasion and escape of antitumor immunosurveillance. Liraglutide, a glucagon-like peptide-1 (GLP-1) analog, is commonly used to treat insulin-resistant diabetes. In t...

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Main Authors: Xian Lu, Chun Xu, Jie Dong, Shuguang Zuo, Hailin Zhang, Chunping Jiang, Junhua Wu, Jiwu Wei
Format: Article
Language:English
Published: Elsevier 2021-01-01
Series:Translational Oncology
Online Access:http://www.sciencedirect.com/science/article/pii/S1936523320303648
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spelling doaj-30fcf25e0114437aa7c09bdcb9a0e1452020-12-25T05:07:28ZengElsevierTranslational Oncology1936-52332021-01-01141100872Liraglutide activates nature killer cell-mediated antitumor responses by inhibiting IL-6/STAT3 signaling in hepatocellular carcinomaXian Lu0Chun Xu1Jie Dong2Shuguang Zuo3Hailin Zhang4Chunping Jiang5Junhua Wu6Jiwu Wei7Jiangsu Key Laboratory of Molecular Medicine, Medical School of Nanjing University, Nanjing 210093, China; Kunshan Hospital of Traditional Chinese Medicine, Kunshan Affiliated Hospital of Nanjing University of Chinese Medicine, Suzhou 215300, ChinaJiangsu Key Laboratory of Molecular Medicine, Medical School of Nanjing University, Nanjing 210093, China; Department of Pathology, School of Medicine, Southeast University, Nanjing 210009, ChinaJiangsu Key Laboratory of Molecular Medicine, Medical School of Nanjing University, Nanjing 210093, ChinaJiangsu Key Laboratory of Molecular Medicine, Medical School of Nanjing University, Nanjing 210093, ChinaJiangsu Key Laboratory of Molecular Medicine, Medical School of Nanjing University, Nanjing 210093, ChinaJiangsu Key Laboratory of Molecular Medicine, Medical School of Nanjing University, Nanjing 210093, China; The Affiliated Drum Hospital, Medical School of Nanjing University, Nanjing 210093, ChinaJiangsu Key Laboratory of Molecular Medicine, Medical School of Nanjing University, Nanjing 210093, China; Corresponding authors.Jiangsu Key Laboratory of Molecular Medicine, Medical School of Nanjing University, Nanjing 210093, China; Corresponding authors.Inflammatory IL-6/STAT3 signaling is constitutively activated in diverse cancers and is associated with malignant cell proliferation, invasion and escape of antitumor immunosurveillance. Liraglutide, a glucagon-like peptide-1 (GLP-1) analog, is commonly used to treat insulin-resistant diabetes. In this study, for the first time, we showed that liraglutide remarkably improved the antitumor immune responses in hepatocellular carcinoma (HCC). Furthermore, we showed that the antitumor activity was mediated by nature killer cells (NKs) but not CD8+ T cells. Finally, we showed that liraglutide enhanced NK-mediated cytotoxicity by suppressing the IL-6/STAT3 signaling pathway in HCC cells. Our findings unveil a novel therapeutic role of liraglutide by manipulating the innate immunity in cancer therapy.http://www.sciencedirect.com/science/article/pii/S1936523320303648
collection DOAJ
language English
format Article
sources DOAJ
author Xian Lu
Chun Xu
Jie Dong
Shuguang Zuo
Hailin Zhang
Chunping Jiang
Junhua Wu
Jiwu Wei
spellingShingle Xian Lu
Chun Xu
Jie Dong
Shuguang Zuo
Hailin Zhang
Chunping Jiang
Junhua Wu
Jiwu Wei
Liraglutide activates nature killer cell-mediated antitumor responses by inhibiting IL-6/STAT3 signaling in hepatocellular carcinoma
Translational Oncology
author_facet Xian Lu
Chun Xu
Jie Dong
Shuguang Zuo
Hailin Zhang
Chunping Jiang
Junhua Wu
Jiwu Wei
author_sort Xian Lu
title Liraglutide activates nature killer cell-mediated antitumor responses by inhibiting IL-6/STAT3 signaling in hepatocellular carcinoma
title_short Liraglutide activates nature killer cell-mediated antitumor responses by inhibiting IL-6/STAT3 signaling in hepatocellular carcinoma
title_full Liraglutide activates nature killer cell-mediated antitumor responses by inhibiting IL-6/STAT3 signaling in hepatocellular carcinoma
title_fullStr Liraglutide activates nature killer cell-mediated antitumor responses by inhibiting IL-6/STAT3 signaling in hepatocellular carcinoma
title_full_unstemmed Liraglutide activates nature killer cell-mediated antitumor responses by inhibiting IL-6/STAT3 signaling in hepatocellular carcinoma
title_sort liraglutide activates nature killer cell-mediated antitumor responses by inhibiting il-6/stat3 signaling in hepatocellular carcinoma
publisher Elsevier
series Translational Oncology
issn 1936-5233
publishDate 2021-01-01
description Inflammatory IL-6/STAT3 signaling is constitutively activated in diverse cancers and is associated with malignant cell proliferation, invasion and escape of antitumor immunosurveillance. Liraglutide, a glucagon-like peptide-1 (GLP-1) analog, is commonly used to treat insulin-resistant diabetes. In this study, for the first time, we showed that liraglutide remarkably improved the antitumor immune responses in hepatocellular carcinoma (HCC). Furthermore, we showed that the antitumor activity was mediated by nature killer cells (NKs) but not CD8+ T cells. Finally, we showed that liraglutide enhanced NK-mediated cytotoxicity by suppressing the IL-6/STAT3 signaling pathway in HCC cells. Our findings unveil a novel therapeutic role of liraglutide by manipulating the innate immunity in cancer therapy.
url http://www.sciencedirect.com/science/article/pii/S1936523320303648
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