HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Regorafenib activates oxidative stress by inhibiting SELENOS and potentiates oxaliplatin-induced cell death in colon cancer cells.

Abstract
Colorectal cancer (CRC) is the third most common cancer, and is one of the leading causes of cancer-related death worldwide. At the time of diagnosis, about 20% of patients with CRC present metastatic disease. Regorafenib, an oral multi-kinase inhibitor, has been demonstrated the efficacy and tolerability in patients with metastatic CRC. Oxaliplatin is a frontline treatment regimen for CRC, and combination treatments with oxaliplatin and other chemotherapeutic agents exert superior therapeutic effects. However, side effects and drug resistance limited their further clinical application. Here, we found that combined treatment with regorafenib and oxaliplatin synergistically enhanced anti-tumor activities in CRC by activating reactive oxygen species (ROS) mediated endoplasmic reticulum (ER) stress, C-Jun-amino-terminal kinase (JNK) and p38 signaling pathways. Regorafenib promoted ROS production by suppressing the expression of selenoprotein S (SELENOS). Knocking down SELENOS sensitized ROS-mediated anti-tumor effects of regorafenib in CRC cells. Furthermore, mouse xenograft models demonstrated that synergistic anti-tumor effects of combined treatment with regorafenib and oxaliplatin. This study provided solid experimental evidences for the combined treatment with regorafenib and oxaliplatin in CRC.
AuthorsYun Yu, Tao Wu, Xiaodong Zhang, Pengfei Li, Lihua Ye, Jiayang Kuang, Lu Tao, Lianli Ni, Qi Zhao, Ji Zhang, Huanle Pan, Congying Xie, Chenguo Zheng, Shaotang Li, Ri Cui
JournalEuropean journal of pharmacology (Eur J Pharmacol) Vol. 957 Pg. 175986 (Oct 15 2023) ISSN: 1879-0712 [Electronic] Netherlands
PMID37598924 (Publication Type: Journal Article)
CopyrightCopyright © 2023 Elsevier B.V. All rights reserved.
Chemical References
  • Oxaliplatin
  • regorafenib
  • Reactive Oxygen Species
Topics
  • Animals
  • Mice
  • Humans
  • Oxaliplatin (pharmacology)
  • Reactive Oxygen Species
  • Colonic Neoplasms (drug therapy)
  • Cell Death
  • Oxidative Stress
  • Disease Models, Animal

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: