EGFR-Targeted Immunotoxin Exerts Antitumor Effects on Esophageal Cancers by Increasing ROS Accumulation and Inducing Apoptosis via Inhibition of the Nrf2-Keap1 Pathway
Joint Authors
Yang, Yun
Tian, Ziyin
Ding, Yanke
Li, Xiaojing
Zhang, Ziheng
Yang, Liu
Zhao, Fangyu
Ren, Feng
Guo, Rui
Source
Journal of Immunology Research
Issue
Vol. 2018, Issue 2018 (31 Dec. 2018), pp.1-10, 10 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2018-11-25
Country of Publication
Egypt
No. of Pages
10
Main Subjects
Abstract EN
Previously, we developed a novel EGFR-targeted antibody (denoted as Pan), which has superior antitumor activity against EGFR-overexpressed tumors.
However, it shows marginal effect on the growth of esophageal cancers.
Therefore, the variable region of Pan was fused to a fragment of Pseudomonas exotoxin A (PE38) to create the immunotoxin, denoted as Ptoxin (PT).
Results indicated that PT shows more effective antitumor activity as compared with Pan both on EGFR-overexpressed KYSE-450 and KYSE-150 esophageal cancer cells, especially on KYSE-450 cells.
Moreover, treatment of PT induces regression of KYSE-450 tumor xenografts in nude mice.
Furthermore, we investigated the potential mechanism involved in the enhanced antitumor effects of PT.
Data showed that PT was more potent in reducing the phosphorylation of EGFR and ERK1/2.
More importantly, we for the first time found that PT was more effective than Pan in inducing ROS accumulation by suppression of the Nrf2-Keap1 antioxidant pathway, and then induced apoptosis in KYSE-450 esophageal cancer cells, which may partly explain the more sensitive response of KYSE-450 to PT treatment.
To conclude, our study provides a promising therapeutic approach for immunotoxin-based esophageal cancer treatment.
American Psychological Association (APA)
Yang, Yun& Tian, Ziyin& Ding, Yanke& Li, Xiaojing& Zhang, Ziheng& Yang, Liu…[et al.]. 2018. EGFR-Targeted Immunotoxin Exerts Antitumor Effects on Esophageal Cancers by Increasing ROS Accumulation and Inducing Apoptosis via Inhibition of the Nrf2-Keap1 Pathway. Journal of Immunology Research،Vol. 2018, no. 2018, pp.1-10.
https://search.emarefa.net/detail/BIM-1191537
Modern Language Association (MLA)
Yang, Yun…[et al.]. EGFR-Targeted Immunotoxin Exerts Antitumor Effects on Esophageal Cancers by Increasing ROS Accumulation and Inducing Apoptosis via Inhibition of the Nrf2-Keap1 Pathway. Journal of Immunology Research No. 2018 (2018), pp.1-10.
https://search.emarefa.net/detail/BIM-1191537
American Medical Association (AMA)
Yang, Yun& Tian, Ziyin& Ding, Yanke& Li, Xiaojing& Zhang, Ziheng& Yang, Liu…[et al.]. EGFR-Targeted Immunotoxin Exerts Antitumor Effects on Esophageal Cancers by Increasing ROS Accumulation and Inducing Apoptosis via Inhibition of the Nrf2-Keap1 Pathway. Journal of Immunology Research. 2018. Vol. 2018, no. 2018, pp.1-10.
https://search.emarefa.net/detail/BIM-1191537
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1191537