Lectin-like oxidized low-density lipoprotein receptor-1 reduces 5-FU sensitivity in gastric cancer cells via...

Area of Science:

• Oncology
• Molecular Biology
• Cancer Research

Background:

• 5-Fluorouracil (5-FU) is a key chemotherapy for advanced gastric cancer (GC).
• Drug resistance is a major challenge, often linked to increased oxidative stress and reactive oxygen species (ROS) in resistant GC cells.
• Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) activation promotes ROS and epithelial-mesenchymal transition in GC.

Purpose of the Study:

• To investigate the role of LOX-1 in 5-FU resistance in advanced gastric cancer.
• To elucidate the molecular mechanisms underlying LOX-1's effect on 5-FU sensitivity.
• To explore LOX-1 as a potential therapeutic target to overcome 5-FU resistance.

Main Methods:

• LOX-1 silencing was performed to assess its impact on 5-FU sensitivity.
• Enrichment analysis and in vitro experiments were used to identify downstream effectors and signaling pathways.
• Bioinformatic predictions and cell-based assays were employed to validate the LOX-1/JAK2/STAT3/NOX4 axis.

Main Results:

• LOX-1 silencing significantly enhanced 5-FU sensitivity, reducing tumor cell viability and colony formation.
• Nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4) was identified as a downstream effector of LOX-1.
• Overexpression of NOX4 reversed the increased 5-FU sensitivity caused by LOX-1 depletion.
• LOX-1 was found to regulate NOX4 expression via the JAK2/STAT3 signaling pathway.

Conclusions:

• The LOX-1 mediated JAK2/STAT3/NOX4 axis is crucial in modulating 5-FU sensitivity in advanced gastric cancer.
• Targeting LOX-1 represents a promising therapeutic strategy to improve the efficacy of 5-FU in treating advanced GC.