ABBS博客分享 http://blog.sciencenet.cn/u/chshou 自由的小鱼

博文

ABBS: Li & EPAC inhibitor ESI-09 suppress pancreatic cancer

已有 1473 次阅读 2019-2-14 17:08 |个人分类:期刊新闻|系统分类:论文交流| EPAC, ESI-09, lithium, GSK3β, pancreatic cancer

Lithium and an EPAC-specific inhibitor ESI-09 synergistically suppress pancreatic cancer cell proliferation and survival

Xinshuo Wang, Cheng Luo, Xiaodong Cheng, and Meiling Lu

State Key Laboratory of Natural Medicines, School of Life Science and Technology, China Pharmaceutical University, Nanjing 210009, China, and Department of Integrative Biology and Pharmacology, Texas Therapeutics Institute, The Brown Foundation Institute of Molecular Medicine, The University of Texas Health Science Center, Houston, TX, USA

Acta Biochim Biophys Sin 2017, 49: 573–580; doi: 10.1093/abbs/gmx045

Our previous studies showed that while lithium suppresses proliferation and induces apoptosis in pancreatic cancer cells, the inhibition of exchange proteins directly activated by cyclic adenosine monophosphate (cAMP) (EPAC)1 blocks pancreatic cancer cell migration and invasion. In this study, we further investigated the combinatory effects of lithium and EPAC-specific inhibitor (ESI)-09, an EPAC-specific inhibitor, on pancreatic cancer cell proliferation and viability, and explored whether lithium synergistically cooperates with EPAC inhibition in suppressing pancreatic cancer cell tumorigenicity. The cell viability of pancreatic cancer cell lines PANC-1 and MiaPaCa-2 was measured after 48 h of incubation with different dose combination of lithium and ESI-09. Flow cytometric analysis was carried out to further verify the impact of lithium and ESI-09 upon PANC-1 cell proliferation and apoptosis. To investigate the mechanism that the effects generated by lithium and ESI-09 on PANC-1 cells, the intracellular cAMP level was measured by an ELISA-based cAMP immunoassay. Our data showed that lithium and ESI-09 synergistically inhibit pancreatic cancer cell growth and survival. Furthermore, our results revealed a novel mechanism in which the synergism between lithium and ESI-09 is not mediated by the inhibitory effect of lithium toward GSK3β, but by lithium's ability to suppress cAMP/protein kinase A signaling.

49-7-578.gif

Combination of LiCl and ESI-09 inhibited the cell proliferation of PANC-1 cells

阅读原文: http://www.abbs.org.cn/arts.asp?id=4172

获取全文: abbs@sibs.ac.cn

相关论文:

1 Epac proteins: multi-purpose cAMP targets

2 Epac: Defining a New Mechanism for cAMP Action

3 A novel Epac-specific cAMP analogue demonstrates independent regulation of Rap1 and ERK

4 The future of EPAC-targeted therapies: agonism versus antagonism

5 Role of Epac2A/Rap1 Signaling in Interplay Between Incretin and Sulfonylurea in Insulin Secretion

6 A Novel EPAC-Specific Inhibitor Suppresses Pancreatic Cancer Cell Migration and Invasion

7 Growth inhibitory effect of lithium gammalinolenate on pancreatic cancer cell lines: The influence of albumin and iron

8 In vivo and in vitro biotransformation of the lithium salt of gamma-linolenic acid by three human carcinomas

8cm.jpg



https://blog.sciencenet.cn/blog-592748-1162182.html

上一篇:ABBS: Citrullination modification by PADI4
下一篇:ABBS: Oxaliplatin inhibits hepatocellular carcinoma
收藏 IP: 202.127.20.*| 热度|

0

该博文允许注册用户评论 请点击登录 评论 (0 个评论)

数据加载中...
扫一扫,分享此博文

Archiver|手机版|科学网 ( 京ICP备07017567号-12 )

GMT+8, 2024-3-29 20:36

Powered by ScienceNet.cn

Copyright © 2007- 中国科学报社

返回顶部