Volume 35, Issue 12 (12-2024)
Studies in Medical Sciences 2024, 35(12): 950-960 |
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Rameshknia V, Movahhedi M, Akhavan A, Valizadeh A, Yousefi B. MELATONIN ENHANCES TOPOTECAN SENSITIVITY IN RESISTANT SW480/TPT COLORECTAL CANCER CELLS. Studies in Medical Sciences 2024; 35 (12) :950-960
URL: http://umj.umsu.ac.ir/article-1-6344-en.html
URL: http://umj.umsu.ac.ir/article-1-6344-en.html
Associate Professor of Clinical Biochemistry, Tabriz University of Medical Sciences, Tabriz, Iran (Corresponding Author) , bahmanusefi@gmail.com
Abstract: (702 Views)
Background & Aims: Chemoresistance, particularly to topotecan (TPT), remains a major obstacle in colorectal cancer treatment. As a topoisomerase I inhibitor, TPT's efficacy is limited by P-glycoprotein (P-gp)-mediated drug resistance. This study examined melatonin's potential to overcome TPT resistance in SW480/TPT cells and its underlying mechanisms.
Materials & Methods: SW480 and drug-resistant SW480/TPT cells were maintained in RPMI-1640/10% FBS. Cells were treated with TPT (0.1-5 μM) alone or combined with melatonin (1-20 μM) in serum-free medium for 48 hours. Apoptosis was quantified using the Cell Death Detection ELISA™ kit. MDR1 expression and P-gp levels were assessed after melatonin treatment (10 μM, 48h). All experiments included ≥3 biological replicates, with data analyzed by one-way ANOVA.
Results: Melatonin synergistically enhanced TPT efficacy, reducing the IC50 from 2.8±0.3 μM to 0.8±0.1 μM (71.4% reduction, p<0.001). Combination therapy increased apoptosis from 15±2% (TPT alone) to 45±4% (3-fold increase, p<0.001). Mechanistically, melatonin downregulated MDR1 expression by 65±5% and decreased P-gp levels by 58±4% versus untreated controls (p<0.001).
Conclusion: Melatonin significantly reverses TPT resistance in colorectal cancer cells by suppressing P-gp/MDR1. These findings position melatonin as a promising adjuvant for combination chemotherapy, warranting further investigation in preclinical models and clinical trials.
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