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.
基金：
National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81673642, 81502032, 81772550]; Beijing Nova ProgramBeijing Municipal Science & Technology Commission [Z181100006218061]; Postdoctoral Science Foundation Program of China [2016M590064]
第一作者机构：[1]Hebei Med Univ, Hosp 4, Res Ctr, Shijiazhuang 050011, Hebei, Peoples R China[2]Chinese Acad Med Sci, Canc Hosp, Natl Canc Ctr, State Key Lab Mol Oncol, Beijing, Peoples R China[3]Peking Union Med Coll, Beijing, Peoples R China
共同第一作者：
通讯作者：
通讯机构：[1]Hebei Med Univ, Hosp 4, Res Ctr, Shijiazhuang 050011, Hebei, Peoples R China[2]Chinese Acad Med Sci, Canc Hosp, Natl Canc Ctr, State Key Lab Mol Oncol, Beijing, Peoples R China[3]Peking Union Med Coll, Beijing, Peoples R China[6]Peking Univ Canc Hosp & Inst, Mol Oncol Lab, Minist Educ, Key Lab Carcinogenesis & Translat Res, Beijing, Peoples R China[*1]Research Centre, The Fourth Hospital of Hebei Medical University, Shijiazhuang, 050011, China[*2]State Key Laboratory of Molecular Oncology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
推荐引用方式(GB/T 7714)：
Zhao Lian-Mei,Li Lei,Huang Ying,et al.Antitumor Effect of Periplocin in TRAIL-Resistant gastric cancer cells via upregulation of death receptor through activating ERK1/2-EGR1 pathway[J].MOLECULAR CARCINOGENESIS.2019,58(6):1033-1045.doi:10.1002/mc.22991.
APA：
Zhao, Lian-Mei,Li, Lei,Huang, Ying,Han, Lu-juan,Li, Dan...&Shan, Bao-En.(2019).Antitumor Effect of Periplocin in TRAIL-Resistant gastric cancer cells via upregulation of death receptor through activating ERK1/2-EGR1 pathway.MOLECULAR CARCINOGENESIS,58,(6)
MLA：
Zhao, Lian-Mei,et al."Antitumor Effect of Periplocin in TRAIL-Resistant gastric cancer cells via upregulation of death receptor through activating ERK1/2-EGR1 pathway".MOLECULAR CARCINOGENESIS 58..6(2019):1033-1045
