Antitumor Effect of Periplocin in TRAIL‐Resistant gastric cancer cells via upregulation of death receptor through activating ERK1/2‐EGR1 pathway
Authors: Li-Yan Xu
Bing-Jie Huo
Ying Huang
Bao-En Shan
Lian-Mei Zhao
Dan Li
Lu-Juan Han
Lei Li
Qimin Zhan
Su-Li Dai
Journal: Molecular Carcinogenesis (2019)
Discipline: CLINICAL MEDICINE
Keywords: ERK1/2-EGR1; TRAIL; death receptors; gastric cancer; periplocin.
Affiliations: Research Centre, The Fourth Hospital of Hebei Medical University, Shijiazhuang, 050011, China., State Key Laboratory of Molecular Oncology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China., Department of Clinical Laboratory, The Fifth Hospital of Shijiazhuang, Shijiazhuang, 050011, China., Department of Biochemistry and Molecular Biology, Medical College of Shantou 4University, Shantou, China., Key laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Laboratory of Molecular Oncology, Peking University Cancer Hospital & Institute, Beijing, China.

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. 

Retracted: No

PubPeer comments:
 Negative control reused in Fig3 D. ![file] , 
 Dear Cicindela Chrysippe Thanks for your comments. Our negative control in this paper was isotype control. Isotype control in Flow cytometry means to use immunoglobulins from the same species source, same subtype, same dose and same immunoglobulin and subtype as the primary antibody to eliminate background staining caused by non-specific binding of antibody to the cell surface. In Figure 3D of our study, SGC-7901 cells were stained with PE-conjugated anti-DR4 mouse antibody (eBioscience) or PE-conjugated anti-DR5 mouse antibody (eBioscience) (Shown in material and method). Both of antibodies are from the same species source, same subtype and same Fluorescent label of PE, so we used the same PE-conjugated mouse IgG1, u03ba Isotype ctrl (eBioscience) in SGC-7901 for negative control (Isotype control)(Shown in material and method). We would like to say that such experimental approach should be reasonable. As shown in figure 3D, we used untreated control group as blank control of experiment, our drug experiments are compared with this group but not negative control (isotype control). Here, we just used isotype control to eliminate background staining caused by non-specific binding of antibody to the cell surface, as described as the usage instruction of isotype control. We highly appreciate your comments and wish our response is able to address the issue you raised. Thanks! ,