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Inhibition of STAT3 Signaling Pathway by Terphenyllin Suppresses Growth and Metastasis of Gastric Cancer

文献类型：期刊论文

作者Yu, Dehua1,2; Qi, Simin1,2; Guan, Xiaoqing1; Yu, Wenkai1,2; Yu, Xuefei1; Cai, Maohua1,2; Li, Qinglin1; Wang, Weiyi5; Zhang, Weidong2,3,4; Qin, Jiang-Jiang1,2
刊名FRONTIERS IN PHARMACOLOGY
出版日期2022-03-25
卷号13
关键词STAT3 inhibitor natural product gastric cancer terphenyllin
DOI10.3389/fphar.2022.870367
通讯作者Wang, Weiyi(wywang@tio.org.cn) ; Zhang, Weidong(wdzhangy@hotmail.com) ; Qin, Jiang-Jiang(jqin@ucas.ac.cn)
英文摘要Gastric cancer is a common type of malignant tumor with a relatively poor prognosis and presents a serious threat to global health. Signal Transducer and Activator of Transcription-3 (STAT3) has been strongly implicated in many cancers, and its constitutive activation promotes growth, angiogenesis, inflammation, and immune evasion. Therefore, considerable efforts have been put into developing effective and safe STAT3 inhibitors. In this study, we performed a virtual screening by molecular docking and found that terphenyllin, a marine-derived natural product, directly interacted with STAT3. We further found that terphenyllin inhibited the phosphorylation and activation of STAT3 and decreased the protein levels of STAT3-dependent target genes, including c-Myc and Cyclin D1. Subsequently, we demonstrated that terphenyllin exerted its potent anticancer efficacy against gastric cancer in vitro and in vivo. Terphenyllin concentration-dependently inhibited growth, proliferation, and colony formation and induced cell cycle arrest and apoptosis of gastric cancer cells in vitro. Moreover, terphenyllin treatment suppressed the tumor growth and metastasis in a gastric cancer orthotopic mouse model without notable toxicity in vivo. Taken together, our results indicated that terphenyllin exerts its anticancer activity by inhibiting the STAT3 signaling pathway and may serve as a potent STAT3 inhibitor for gastric cancer treatment.
WOS关键词MDM2 INHIBITOR ; BREAST-CANCER ; IDENTIFICATION ; DELIVERY ; TARGET
资助项目Program of Zhejiang Provincial TCM Sci-tech Plan[2020ZZ005] ; National Key R and D Program of China[2021YFA0910100] ; National Natural Science Foundation of China[81903842] ; Natural Science Foundation of Zhejiang Province[LR21H280001] ; Natural Science Foundation of Zhejiang Province[LQ22H280022] ; Natural Science Foundation of Fujian Province[2021J01509] ; China Postdoctoral Science Foundation[2021M692873] ; Scientific Research Foundation of Third Institute of Oceanography SOA[2018021]
WOS研究方向Pharmacology & Pharmacy
语种英语
出版者FRONTIERS MEDIA SA
WOS记录号WOS:000792231200001
资助机构Program of Zhejiang Provincial TCM Sci-tech Plan ; National Key R and D Program of China ; National Natural Science Foundation of China ; Natural Science Foundation of Zhejiang Province ; Natural Science Foundation of Fujian Province ; China Postdoctoral Science Foundation ; Scientific Research Foundation of Third Institute of Oceanography SOA
源URL[http://ir.hfcas.ac.cn:8080/handle/334002/130813]  
专题中国科学院合肥物质科学研究院
通讯作者Wang, Weiyi; Zhang, Weidong; Qin, Jiang-Jiang
作者单位1.Univ Chinese Acad Sci, Chinese Acad Sci, Canc Hosp, Zhejiang Canc Hosp,Inst Basic Med & Canc IBMC, Hangzhou, Peoples R China
2.Zhejiang Chinese Med Univ, Coll Pharmaceut Sci, Hangzhou, Peoples R China
3.Second Mil Med Univ, Sch Pharm, Shanghai, Peoples R China
4.Shanghai Univ Tradit Chinese Med, Inst Interdisciplinary Integrat Med Res & Shuguan, Shanghai, Peoples R China
5.Minist Nat Resources, Key Lab Marine Biogenet Resources, Third Inst Oceanog, Xiamen, Peoples R China
推荐引用方式
GB/T 7714		 Yu, Dehua,Qi, Simin,Guan, Xiaoqing,et al. Inhibition of STAT3 Signaling Pathway by Terphenyllin Suppresses Growth and Metastasis of Gastric Cancer[J]. FRONTIERS IN PHARMACOLOGY,2022,13.
APA Yu, Dehua.,Qi, Simin.,Guan, Xiaoqing.,Yu, Wenkai.,Yu, Xuefei.,...&Qin, Jiang-Jiang.(2022).Inhibition of STAT3 Signaling Pathway by Terphenyllin Suppresses Growth and Metastasis of Gastric Cancer.FRONTIERS IN PHARMACOLOGY,13.
MLA Yu, Dehua,et al."Inhibition of STAT3 Signaling Pathway by Terphenyllin Suppresses Growth and Metastasis of Gastric Cancer".FRONTIERS IN PHARMACOLOGY 13(2022).

入库方式： OAI收割

来源：合肥物质科学研究院

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