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

doi:10.3389/fphar.2022.870367

	Inhibition of STAT3 Signaling Pathway by Terphenyllin Suppresses Growth and Metastasis of Gastric Cancer
	Yu, Dehua 1,4; Qi, Simin 1,4; Guan, Xiaoqing 1; Yu, Wenkai 1,4; Yu, Xuefei 1; Cai, Maohua 1,4; Li, Qinglin 1; Wang, Weiyi 5; Zhang, Weidong 2,3,4; Qin, Jiang-Jiang 1,4
刊名	FRONTIERS IN PHARMACOLOGY
	2022-03-25
卷号	13
关键词	STAT3 inhibitor natural product gastric cancer terphenyllin
DOI	10.3389/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.
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关键词	MDM2 INHIBITOR ; BREAST-CANCER ; IDENTIFICATION ; DELIVERY ; TARGET
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
内容类型	期刊论文
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.Shanghai Univ Tradit Chinese Med, Inst Interdisciplinary Integrat Med Res & Shuguan, Shanghai, Peoples R China 3.Second Mil Med Univ, Sch Pharm, Shanghai, Peoples R China 4.Zhejiang Chinese Med Univ, Coll Pharmaceut Sci, Hangzhou, 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).