Year: 2024
Type: article
Abstract: 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.
Source: Studies in Medical Sciences
Authors: Vahid Rameshknia, Moireh Movahhedi, Abbas Akhavan, Amir Valizadeh, Bahman Yousefi
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
OpenAlex ID: W4410078725