title: Embelin inhibits pancreatic cancer progression by directly inducing cancer cell apoptosis and indirectly restricting IL-6 associated inflammatory and immune suppressive cells.
abstract: Pancreatic cancer is an aggressive malignancy and unresponsive to conventional chemotherapies. Here, the anti-inflammatory and anti-tumor effects of embelin on pancreatic cancer were investigated. Embelin significantly attenuated cells invasion, proliferation and induced apoptosis through inhibition of STAT3 and activation of p53 signaling pathways. Embelin substantially reduced the tumorigenicity of pancreatic cancer cells in vivo, which was associated with reduced inflammatory cells and immune suppressive cells, IL-17A(+) Th17, GM-CSF(+) Th, MDSCs and Treg, through inhibition of IL-6 secretion. Moreover, embelin decrease IL-6-induced STAT3 phosphorylation. In summary, embelin represents a novel therapeutic drug candidate for the clinical treatment of pancreatic cancer.
authors.affiliation: Laboratory of Immunology and Inflammation, Research Center of Basic Medical Science, Tianjin Medical University, Tianjin, China; Department of Immunology, Basic Medical College, Tianjin Medical University, Tianjin, China; Key Laboratory of Immune Microenvironment and Diseases of Educational Ministry of China, Tianjin Medical University, Tianjin, China; Department of Immunology, Basic Medical College, Weifang Medical University, Weifang, China.
authors.forename: Meiyu
authors.initials: M
authors.lastname: Peng
authors.affiliation: Laboratory of Immunology and Inflammation, Research Center of Basic Medical Science, Tianjin Medical University, Tianjin, China; Department of Immunology, Basic Medical College, Tianjin Medical University, Tianjin, China; Key Laboratory of Immune Microenvironment and Diseases of Educational Ministry of China, Tianjin Medical University, Tianjin, China.
authors.forename: Bingqing
authors.initials: B
authors.lastname: Huang
authors.affiliation: Department of Pharmacology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Laboratory of Immunology and Inflammation, Research Center of Basic Medical Science, Tianjin Medical University, Tianjin, China; Department of Immunology, Basic Medical College, Tianjin Medical University, Tianjin, China; Key Laboratory of Immune Microenvironment and Diseases of Educational Ministry of China, Tianjin Medical University, Tianjin, China.
authors.forename: Shuyu
authors.initials: S
authors.lastname: Fu
authors.affiliation: Laboratory of Immunology and Inflammation, Research Center of Basic Medical Science, Tianjin Medical University, Tianjin, China; Department of Immunology, Basic Medical College, Tianjin Medical University, Tianjin, China; Key Laboratory of Immune Microenvironment and Diseases of Educational Ministry of China, Tianjin Medical University, Tianjin, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Wang
authors.affiliation: Laboratory of Immunology and Inflammation, Research Center of Basic Medical Science, Tianjin Medical University, Tianjin, China; Department of Immunology, Basic Medical College, Tianjin Medical University, Tianjin, China; Key Laboratory of Immune Microenvironment and Diseases of Educational Ministry of China, Tianjin Medical University, Tianjin, China.
authors.forename: Xixi
authors.initials: X
authors.lastname: Cheng
authors.affiliation: Laboratory of Immunology and Inflammation, Research Center of Basic Medical Science, Tianjin Medical University, Tianjin, China; Department of Immunology, Basic Medical College, Tianjin Medical University, Tianjin, China; Key Laboratory of Immune Microenvironment and Diseases of Educational Ministry of China, Tianjin Medical University, Tianjin, China.
authors.forename: Xi
authors.initials: X
authors.lastname: Wu
authors.affiliation: Laboratory of Immunology and Inflammation, Research Center of Basic Medical Science, Tianjin Medical University, Tianjin, China; Department of Immunology, Basic Medical College, Tianjin Medical University, Tianjin, China; Key Laboratory of Immune Microenvironment and Diseases of Educational Ministry of China, Tianjin Medical University, Tianjin, China.
authors.forename: Zhenyi
authors.initials: Z
authors.lastname: Xue
authors.affiliation: Laboratory of Immunology and Inflammation, Research Center of Basic Medical Science, Tianjin Medical University, Tianjin, China; Department of Immunology, Basic Medical College, Tianjin Medical University, Tianjin, China; Key Laboratory of Immune Microenvironment and Diseases of Educational Ministry of China, Tianjin Medical University, Tianjin, China.
authors.forename: Lijuan
authors.initials: L
authors.lastname: Zhang
authors.affiliation: School of Medical Imaging, Tianjin Medical University, Tianjin 300070, China.
authors.forename: Da
authors.initials: D
authors.lastname: Zhang
authors.affiliation: Laboratory of Immunology and Inflammation, Research Center of Basic Medical Science, Tianjin Medical University, Tianjin, China; Department of Immunology, Basic Medical College, Tianjin Medical University, Tianjin, China; Key Laboratory of Immune Microenvironment and Diseases of Educational Ministry of China, Tianjin Medical University, Tianjin, China.
authors.forename: Yurong
authors.initials: Y
authors.lastname: Da
authors.affiliation: Department of Gastroenterology, Peking University First Hospital, Beijing, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Dai
authors.affiliation: Department of Genitourinary Oncology, Tianjin Medical University Cancer Hospital, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Yang
authors.affiliation: Laboratory of Immunology and Inflammation, Research Center of Basic Medical Science, Tianjin Medical University, Tianjin, China; Department of Immunology, Basic Medical College, Tianjin Medical University, Tianjin, China; Key Laboratory of Immune Microenvironment and Diseases of Educational Ministry of China, Tianjin Medical University, Tianjin, China.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Yao
authors.affiliation: Storr Liver Unit, Westmead Millennium Institute, The Western Clinical School of the University of Sydney, Westmead Hospital, Westmead, NSW 2145, Australia. Electronic address: liang.qiao@sydney.edu.au.
authors.forename: Liang
authors.initials: L
authors.lastname: Qiao
authors.affiliation: Laboratory of Immunology and Inflammation, Research Center of Basic Medical Science, Tianjin Medical University, Tianjin, China; Department of Immunology, Basic Medical College, Tianjin Medical University, Tianjin, China; Key Laboratory of Immune Microenvironment and Diseases of Educational Ministry of China, Tianjin Medical University, Tianjin, China. Electronic address: rongxinz@yahoo.com.
authors.forename: Rongxin
authors.initials: R
authors.lastname: Zhang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D016227:Benzoquinones / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004195:Disease Models, Animal; D018450:Disease Progression; D015536:Down-Regulation; D005260:Female; D007249:Inflammation / Q000188:drug therapy / Q000276:immunology / Q000473:pathology; D015850:Interleukin-6 / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000276:immunology* / Q000473:pathology; D050796:STAT3 Transcription Factor / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D016227:Benzoquinones; D015850:Interleukin-6; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; D016159:Tumor Suppressor Protein p53; C010945:embelin
keywords: Embelin; IL-6; Inflammation; MDSCs; Pancreatic cancer