title: Wogonin Inhibits Tumor-derived Regulatory Molecules by Suppressing STAT3 Signaling to Promote Tumor Immunity.
abstract: Wogonin exerts effective antitumor activities through direct cytotoxicity against cancer cells and indirect immune modulation. However, the molecular mechanisms of these activities remain poorly understood and need further study. We found that wogonin could efficiently downregulate the expression of B7H1, retinoic acid early induced transcript-1ε (RAE-1ε), and vascular endothelial growth factor in gastric cancer cells. Wogonin also promoted the secretion of calreticulin and high-mobility group protein 1 by tumor cells. Apoptotic bodies from dying tumor cells treated with wogonin were susceptible for uptake by neighboring dendritic cells (DCs). With the xenograft tumor model, wogonin inhibited tumor growth and promoted the recruitment of DC, T, and NK cells into tumor tissues. Infiltrated frequencies of DC, T, and NK cells in tumors were inversely correlated with expression levels of vascular endothelial growth factor, B7H1, and RAE-1ε of tumor tissues. Wogonin directly inhibited the activation of STAT3 on tyrosine 705 in tumor cells. The dephosphorylation of STAT3 contributed to the decreased expression of B7H1 and MHC class I chain-related protein A, and the enhancement of calreticulin on the cell membrane. Our study confirmed the immune-enhancing function of wogonin, and indicated that wogonin could be used in collaboration with DC vaccine or activated lymphocytes for tumor therapy.
authors.affiliation: *Department of Gastroenterology, The Second Clinical Medical College ‡Department of Immunology, School of Medicine, Yangzhou University †Jiangsu Key Laboratory of Integrated Traditional Chinese, Western Medicine for Prevention and Treatment of Senile Diseases §Jiangsu Key Laboratory of Zoonosis ∥Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonosis, Yangzhou, P.R. China.
authors.forename: Weiming
authors.initials: W
authors.lastname: Xiao
authors.forename: Keyan
authors.initials: K
authors.lastname: Wu
authors.forename: Min
authors.initials: M
authors.lastname: Yin
authors.forename: Sen
authors.initials: S
authors.lastname: Han
authors.forename: Yanbing
authors.initials: Y
authors.lastname: Ding
authors.forename: Ahui
authors.initials: A
authors.lastname: Qiao
authors.forename: Guotao
authors.initials: G
authors.lastname: Lu
authors.forename: Bing
authors.initials: B
authors.lastname: Deng
authors.forename: Ping
authors.initials: P
authors.lastname: Bo
authors.forename: Weijuan
authors.initials: W
authors.lastname: Gong
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D060890:B7-H1 Antigen / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D004195:Disease Models, Animal; D015536:Down-Regulation; D044950:Flavanones / Q000494:pharmacology*; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000378:metabolism; D006801:Humans; D056747:Immunomodulation / Q000187:drug effects*; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology / Q000378:metabolism; D051379:Mice; D009369:Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000276:immunology* / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D010587:Phagocytosis / Q000187:drug effects; D010766:Phosphorylation; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D060890:B7-H1 Antigen; D044950:Flavanones; D015395:Histocompatibility Antigens Class I; C099187:MHC class I-related chain A; D050796:STAT3 Transcription Factor; D042461:Vascular Endothelial Growth Factor A; C085514:wogonin