Regorafenib inhibited gastric cancer cells growth and invasion via CXCR4 activated Wnt pathway.

Abstract

AIM:

Regorafenib is an oral small-molecule multi kinase inhibitor. Recently, several clinical trials have revealed that regorafenib has an anti-tumor activity in gastric cancer. However, only part of patients benefit from regorafenib, and the mechanisms of regorafenib's anti-tumor effect need further demonstrating. In this study, we would assess the potential anti-tumor effects and the underlying mechanisms of regorafenib in gastric cancer cells, and explore novel biomarkers for patients selecting of regorafenib.

METHODS:

The anti-tumor effects of regorafenib on gastric cancer cells were analyzed via cell proliferation and invasion. The underlying mechanisms were demonstrated using molecular biology techniques.

RESULTS:

We found that regorafenib inhibited cell proliferation and invasion at the concentration of 20μmol/L and in a dose dependent manner. The anti-tumor effects of regorafenib related to the decreased expression of CXCR4, and elevated expression and activation of CXCR4 could reverse the inhibition effect of regorafenib on gastric cancer cells. Further studies revealed that regorafenib reduced the transcriptional activity of Wnt/β-Catenin pathway and led to decreased expression of Wnt pathway target genes, while overexpression and activation of CXCR4 could attenuate the inhibition effect of regorafenib on Wnt/β-Catenin pathway.

CONCLUSIONS:

Our findings demonstrated that regorafenib effectively inhibited cell proliferation and invasion of gastric cancer cells via decreasing the expression of CXCR4 and further reducing the transcriptional activity of Wnt/β-Catenin pathway.

• Authors: Xiao-Lin Lin, Qi Xu, Lei Tang, Li Sun, Ting Han, Li-Wei Wang, Xiu-Ying Xiao
• Journal: PloS one (PLoS One) Vol. 12 Issue 5 Pg. e0177335 ( 2017) ISSN: 1932-6203 [Electronic] United States
• PMID: 28489887 (Publication Type: Journal Article)

Chemical References

• Antineoplastic Agents
• CXCR4 protein, human
• Phenylurea Compounds
• Pyridines
• Receptors, CXCR4
• regorafenib

Topics

• Antineoplastic Agents (pharmacology)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Gastric Mucosa (metabolism)
• Humans
• Phenylurea Compounds (pharmacology)
• Pyridines (pharmacology)
• Receptors, CXCR4 (metabolism)
• Stomach (drug effects, pathology)
• Stomach Neoplasms (drug therapy, metabolism, pathology)
• Wnt Signaling Pathway (drug effects)