Antitumor Effect of Periplocin in TRAIL-Resistant gastric cancer cells via upregulation of death receptor through activating ERK1/2-EGR1 pathway.

Abstract:

:Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), a member of the tumor necrosis factor family, induces apoptosis in a variety of cancer cells. However, gastric cancer (GC) cells are insensitive to TRAIL usually. In the previous study, we showed that Periplocin could induce apoptosis in GC cells via the activation of ERK1/2-EGR1 pathway. In the present study, we have shown that the combination of Periplocin and TRAIL had a greater inhibitory effect on gastric cancer cell viability in vitro and in vivo than Periplocin or TRAIL alone. Through upregulating the expression of DR4 and DR5 at transcriptional and protein levels, Periplocin enhanced the sensitivity of gastric cancer cells to TRAIL. Furthermore, enhanced activity of ERK1/2-EGR1 pathway was responsible for upregulating of DR4 and DR5 uponPeriplocin treatment, subsequently reducing the expression of Mcl-1 and Bcl2 and activating Bid and caspase-3/8. Collectively, these data implied that Periplocin might act as a sensitizer of TRAIL and could be a potential strategy for the treatment of GC.

journal_name

Mol Carcinog

journal_title

Molecular carcinogenesis

authors

Zhao LM,Li L,Huang Y,Han LJ,Li D,Huo BJ,Dai SL,Xu LY,Zhan Q,Shan BE

doi

10.1002/mc.22991

subject

Has Abstract

pub_date

2019-06-01 00:00:00

pages

1033-1045

issue

6

eissn

0899-1987

issn

1098-2744

journal_volume

58

pub_type

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