Terphenyllin Suppresses Orthotopic Pancreatic Tumor Growth and Prevents Metastasis in Mice

doi:10.3389/fphar.2020.00457

HFCAS OpenIR

	Terphenyllin Suppresses Orthotopic Pancreatic Tumor Growth and Prevents Metastasis in Mice
	Zhang, Jia 1,2; Wang, Weiyi 3; Zhou, Yuan 2; Yang, Jing 2; Xu, Jingli 4; Xu, Zhiyuan 5,6,7; Xu, Beihua 2; Yan, Li 8; Cheng, Xiang-Dong 5,6,7; Li, Minghua 1; Qin, Jiang-Jiang 2,5,6,7
	2020-04-08
发表期刊	FRONTIERS IN PHARMACOLOGY
ISSN	1663-9812
通讯作者	Wang, Weiyi(wywang@tio.org.cn) ; Li, Minghua(1035448060@qq.com) ; Qin, Jiang-Jiang(jqin@zcmu.edu.cn)
摘要	Pancreatic cancer (PC) is an aggressive and fatal disease with high incidences of metastasis and recurrence. However, there are no effective treatment options for the majority of PC patients, especially for those with locally advanced tumors and metastatic diseases. Therefore, it is urgently needed to develop safe and effective anti-PC therapeutic agents. We have recently identified a novel marine-derived natural product terphenyllin with potent anti-PC activity. The present study was designed to investigate the efficacy and mechanisms of action of terphenyllin in several human PC cell lines and an orthotopic PC mouse model. The results showed that terphenyllin significantly inhibited the viability of all PC cell lines with minimal effects on a normal human pancreatic cell line (HPNE). We next demonstrated the effects of terphenyllin on colony formation, apoptosis, migration, and invasion in both Panc1 and HPAC cell lines in a concentration-dependent manner. Terphenyllin also suppressed the tumor growth and metastasis in the Panc1 orthotopic mouse model. We further showed the profound effects of terphenyllin on the expression of apoptosis-associated proteins, including Bax, Bad, Puma, Bim(L), Bcl-2, phos-Bcl-2 (Ser70), Bcl-xL, caspase 7, and PARP, which contributed to its anti-PC activity. In summary, terphenyllin suppressed the PC cell growth and metastasis in vitro and in vivo and may be developed as an anti-PC therapeutic agent in the future.
关键词	terphenyllin pancreatic cancer metastasis Bax Bcl-2 Puma
DOI	10.3389/fphar.2020.00457
关键词[WOS]	MDM2 INHIBITOR ; IN-VITRO ; CANCER ; THERAPY ; IDENTIFICATION ; SURVIVAL ; TARGET ; GEMCITABINE ; PACLITAXEL ; FOLFIRINOX
收录类别	SCI
语种	英语
资助项目	National Natural Science Foundation of China[81903842] ; National Natural Science Foundation of China[81573953] ; Program of Zhejiang Provincial TCM Sci-tech Plan[2020ZZ005] ; Program of Zhejiang Provincial TCM Sci-tech Plan[2016ZZ012] ; Zhejiang Chinese Medical University[111100E014] ; Medical Science and Technology Project of Zhejiang Province[WKJ-ZJ-1728] ; Traditional Chinese Medical Science and Technology Major Project of Zhejiang Province[2018ZY006] ; Science and Technology Projects of Zhejiang Province[2019C03049] ; Foundation of Third Institute of Oceanography SOA[2017001] ; Foundation of Third Institute of Oceanography SOA[2018021] ; Natural Science Foundation of Fujian Province[2018J01064] ; COMRA program[DY135-B2-05] ; COMRA program[DY135-B2-01]
项目资助者	National Natural Science Foundation of China ; Program of Zhejiang Provincial TCM Sci-tech Plan ; Zhejiang Chinese Medical University ; Medical Science and Technology Project of Zhejiang Province ; Traditional Chinese Medical Science and Technology Major Project of Zhejiang Province ; Science and Technology Projects of Zhejiang Province ; Foundation of Third Institute of Oceanography SOA ; Natural Science Foundation of Fujian Province ; COMRA program
WOS研究方向	Pharmacology & Pharmacy
WOS类目	Pharmacology & Pharmacy
WOS记录号	WOS:000529501700001
出版者	FRONTIERS MEDIA SA
引用统计	被引频次：18[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	http://ir.hfcas.ac.cn:8080/handle/334002/103432
专题	中国科学院合肥物质科学研究院
通讯作者	Wang, Weiyi; Li, Minghua; Qin, Jiang-Jiang
作者单位	1.Shanxi Prov Acad Tradit Chinese Med, Taiyuan, Peoples R China 2.Zhejiang Chinese Med Univ, Coll Pharmaceut Sci, Hangzhou, Peoples R China 3.Minist Nat Resources, Inst Oceanog 3, Key Lab Marine Biogenet Resources, Xiamen, Peoples R China 4.Zhejiang Chinese Med Univ, Clin Med Coll 1, Hangzhou, Peoples R China 5.Chinese Acad Sci, Inst Canc & Basic Med, Hangzhou, Peoples R China 6.Univ Chinese Acad Sci, Canc Hosp, Hangzhou, Peoples R China 7.Zhejiang Canc Hosp, Hangzhou, Peoples R China 8.Naval Med Univ, Sch Pharm, Shanghai, Peoples R China
推荐引用方式 GB/T 7714	Zhang, Jia,Wang, Weiyi,Zhou, Yuan,et al. Terphenyllin Suppresses Orthotopic Pancreatic Tumor Growth and Prevents Metastasis in Mice[J]. FRONTIERS IN PHARMACOLOGY,2020,11.
APA	Zhang, Jia.,Wang, Weiyi.,Zhou, Yuan.,Yang, Jing.,Xu, Jingli.,...&Qin, Jiang-Jiang.(2020).Terphenyllin Suppresses Orthotopic Pancreatic Tumor Growth and Prevents Metastasis in Mice.FRONTIERS IN PHARMACOLOGY,11.
MLA	Zhang, Jia,et al."Terphenyllin Suppresses Orthotopic Pancreatic Tumor Growth and Prevents Metastasis in Mice".FRONTIERS IN PHARMACOLOGY 11(2020).