H1, a derivative of tetrandrine, enhances the efficacy of 5-FU in Bel7402/5-FU cells via suppressing STAT3/MCL-1 and inducing PUMA

doi:10.1016/j.bbrc.2019.09.082

CORC > 海洋研究所 > 中国科学院海洋研究所 > 实验海洋生物学重点实验室

	H1, a derivative of tetrandrine, enhances the efficacy of 5-FU in Bel7402/5-FU cells via suppressing STAT3/MCL-1 and inducing PUMA
	Li, Fengli 1; Wang, Jing 2; Wu, Ning 3,4; Zhang, Hua 5; Li, Zheng 1; Wei, Ning 6,7
刊名	BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
	2019-11-26
卷号	520 期号:1 页码:93-98
关键词	5-FU Drug resistance STAT3 Hepatocellular carcinoma MCL-1 PUMA
ISSN号	0006-291X
DOI	10.1016/j.bbrc.2019.09.082
通讯作者	Wang, Jing(wangjing2006050@126.com) ; Wei, Ning(chinaweining@yahoo.com)
英文摘要	Currently, 5-fluorouracil (5-FU) resistance became a major obstacle to its clinical use for patients with hepatocellular carcinoma (HCC). It's urgent to develop a novel strategy for enhancing the therapeutic efficacy of 5-FU. Herein, we found that H1 (a derivative of Tetrandrine) exerted a potent anti-MDR effect on growth of 5-FU resistant HCC cells (Be17402/5FU). The resistant fold (RF) of 5-FU is over 160-fold, while the RF of H1 is only 4.8-fold in Be17402/5-FU cells. Further studies demonstrated that blockage of STAT3/MCL-1 signaling and induction of PUMA is responsible to anti-MDR activity of H1. Moreover, combination of H1 and 5-FU (Ratio = 1:2) could synergistically induce apoptosis of Be17402/5-FU cells. Co-treatment of H1 enhances the suppression of p-STAT3 and MCL-1, and significantly increases PUMA expression. Finally, the combination of H1 and 5-FU results in an increase of cleaved PARP. Taken together, H1 effectively improve the cytotoxic effect of 5-FU against Be17402/5-FU cells via blocking STAT3/MCL-1 pathway and inducing PUMA. Our findings suggested that combination 5-FU with anti-MDR agents might present a novel strategy to enhance the therapeutic efficacy of 5-FU in resistant HCC. (C) 2019 Elsevier Inc. All rights reserved.
资助项目	China National Natural Sciences Foundation[81202556]
WOS研究方向	Biochemistry & Molecular Biology ; Biophysics
语种	英语
出版者	ACADEMIC PRESS INC ELSEVIER SCIENCE
WOS记录号	WOS:000506410000015
内容类型	期刊论文
源URL	[http://ir.qdio.ac.cn/handle/337002/164172]
专题	海洋研究所_实验海洋生物学重点实验室
通讯作者	Wang, Jing; Wei, Ning
作者单位	1.Tianjin Univ Tradit Chinese Med, Teaching Hosp 1, Tianjin, Peoples R China 2.Jinzhou Med Univ, Affiliated Hosp 1, Jinzhou, Peoples R China 3.Chinese Acad Sci, Inst Oceanol, Key Lab Expt Marine Biol, Qingdao, Peoples R China 4.Qingdao Natl Lab Marine Sci & Technol, Lab Marine Drugs & Bioprod, Qingdao, Peoples R China 5.Jinzhou Med Univ, Jinzhou, Peoples R China 6.Univ Pittsburgh, Sch Med, Dept Med, Div Hematol Oncol, Pittsburgh, PA 15232 USA 7.Univ Pittsburgh, UPMC Hillman Canc Ctr, Canc Therapeut Program, Pittsburgh, PA 15232 USA
推荐引用方式 GB/T 7714	Li, Fengli,Wang, Jing,Wu, Ning,et al. H1, a derivative of tetrandrine, enhances the efficacy of 5-FU in Bel7402/5-FU cells via suppressing STAT3/MCL-1 and inducing PUMA[J]. BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS,2019,520(1):93-98.
APA	Li, Fengli,Wang, Jing,Wu, Ning,Zhang, Hua,Li, Zheng,&Wei, Ning.(2019).H1, a derivative of tetrandrine, enhances the efficacy of 5-FU in Bel7402/5-FU cells via suppressing STAT3/MCL-1 and inducing PUMA.BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS,520(1),93-98.
MLA	Li, Fengli,et al."H1, a derivative of tetrandrine, enhances the efficacy of 5-FU in Bel7402/5-FU cells via suppressing STAT3/MCL-1 and inducing PUMA".BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 520.1(2019):93-98.