This study investigated the combined effects of agomelatine, a melatonergic antidepressant, and cetuximab, an EGFR inhibitor, on the colorectal cancer cell line (Caco-2). Caco-2 cells were treated with agomelatine (0.3 μg/ml and 3 μg/ml) and cetuximab (50 μg/ml), individually and in combination, for 24 and 48 hours. Cell viability was assessed using the MTT assay. Gene expression analysis of EGFR, BCL2, PIK3CA, BAX, mTOR, and AKT3 was performed using real-time PCR. All treatment groups showed significant decreases in cell viability compared to the control (p<0.05), with enhanced effects in combined treatments. EGFR expression was significantly reduced in drug-treated groups, particularly with cetuximab (p<0.05). While changes were observed in BCL2, PIK3CA, BAX, mTOR, and AKT3 expression, these were not statistically significant (p>0.05). This study demonstrates the potential synergistic cytotoxic effects of agomelatine and cetuximab on Caco-2 colorectal cancer cells. The significant reduction in EGFR expression suggests a potential mechanism of action. These findings provide insights into combining chemotherapeutic agents with drugs addressing circadian rhythm disorders in CRC treatment strategies. Further research is warranted to elucidate the clinical implications of these observations.
Colorectal Cancer Cetuximab Agomelatine PI3K/AKT/mTOR pathway Gene Expression Chemotherapy Antidepressants Combined Therapy.
Primary Language | English |
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Subjects | Structural Biology |
Journal Section | Research Articles |
Authors | |
Early Pub Date | December 19, 2024 |
Publication Date | |
Submission Date | February 26, 2024 |
Acceptance Date | September 16, 2024 |
Published in Issue | Year 2024 Volume: 9 Issue: 3 |